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Bui, H.B.; Inaba, K. Zinc Transporters in Different Biological Kingdoms. Encyclopedia. Available online: https://encyclopedia.pub/entry/56105 (accessed on 18 May 2024).
Bui HB, Inaba K. Zinc Transporters in Different Biological Kingdoms. Encyclopedia. Available at: https://encyclopedia.pub/entry/56105. Accessed May 18, 2024.
Bui, Han Ba, Kenji Inaba. "Zinc Transporters in Different Biological Kingdoms" Encyclopedia, https://encyclopedia.pub/entry/56105 (accessed May 18, 2024).
Bui, H.B., & Inaba, K. (2024, March 11). Zinc Transporters in Different Biological Kingdoms. In Encyclopedia. https://encyclopedia.pub/entry/56105
Bui, Han Ba and Kenji Inaba. "Zinc Transporters in Different Biological Kingdoms." Encyclopedia. Web. 11 March, 2024.
Zinc Transporters in Different Biological Kingdoms
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This entry is adapted from the peer-reviewed paper 10.3390/ijms25053045

Zinc transporters take up/release zinc ions (Zn2+) across biological membranes and maintain intracellular and intra-organellar Zn2+ homeostasis. Since this process requires a series of conformational changes in the transporters, detailed information about the structures of different reaction intermediates is required for a comprehensive understanding of their Zn2+ transport mechanisms. Various Zn2+ transport systems have been identified in bacteria, yeasts, plants, and humans. 

zinc transporter ZnT cryo-EM

1. Introduction

Zinc ions (Zn2+), an essential trace element in bacteria, fungi, plants, and animals, including humans [1], serve as a key component in many signal transduction processes and act as an essential cofactor for many proteins and enzymes [2][3]. Zinc deficiency causes several human diseases [4][5][6][7][8][9][10][11][12][13]; indeed, zinc supplements have beneficial effects on human health [8][14][15][16][17][18][19]. However, excessive adsorption of Zn2+ leads to disruption of the gastrointestinal flora balance, deficiency of other essential heavy metals, including iron, copper, and manganese, and reduction in immune function [20][21][22][23]. Zn2+ also plays an important role in the physiology of organisms such as plants and bacteria [24][25]. In plants, zinc deficiency is linked to growth defects and inhibition of flowering [26][27]. Additionally, Zn2+ is responsible for the virulence of some bacteria [28]. Since Zn2+ is involved in numerous biological events, humans, plants, yeasts, and bacteria have evolved elaborate Zn2+ transport systems that respond to Zn2+ perturbation.
Failure of the Zn2+ transport systems plays a role in diseases such as cancer [29][30], Alzheimer’s [31][32], and Parkinson’s [33][34], as well as temporary zinc deficiency in newborns [35], perinatal fatal cardiomyopathy [36], risk of febrile seizures [37], Lowe’s syndrome [38], disorders of muscle tone with polycythemia [39][40], and chronic liver disease [40]. Therefore, human zinc transporters (ZnTs) are potential targets of drugs and preclinical diagnostic tests. Owing to the important physiological roles, and pharmacological and preclinical diagnostic significance of Zn2+ transport systems, a variety of biochemical, structural, physiological, and genetic experiments have been carried out over the past several decades to better understand their functions and mechanisms. The most comprehensively studied bacterial zinc transporter is YiiP, which works in Escherichia coli and Shewanella oneidensis (EcYiiP and SoYiiP, respectively) [41][42][43][44][45][46][47][48][49]. These transporters are a convenient model to study the general mechanisms underlying Zn2+ transport. The most intensively studied mammalian ZnTs are SLC30A7/ZnT7 [50] and SLC30A8/ZnT8 [51][52]. Researchers' interests in ZnT family members stem mainly from their roles in maintaining Zn2+ homeostasis in cellular organelles throughout the body and the fact that their dysfunction causes serious diseases.
As is the case for other membrane transporters, ZnTs undergo conformational conversion to transport Zn2+ across biological membranes. To fully understand the mechanism underlying Zn2+ transport, high-resolution structures of the transporters have been captured in different states. The first X-ray crystal structure of a zinc transporter (Table 1) was reported for EcYiiP [41][42], followed by the EM structure of SoYiiP [43][44][45][46]. More recently, cryo-EM structures of vertebrate ZnTs have been reported (Table 1); these include Homo sapiens ZnT7 (HsZnT7) [50], Homo sapiens ZnT8 (HsZnT8) [51], and Xenopus tropicalis ZnT8 (XtZnT8) [52]. These structures allow us to propose an updated model of ZnTs-mediated Zn2+ transport. Of note, researchers' recent structural and biochemical studies on HsZnT7 revealed the role of its cytosolic histidine-rich loop (His-loop) in efficient Zn2+ uptake [50]. Thus, researchers have built on the structural and mechanistic foundations of ZnTs in the biological kingdom, while making significant progress regarding research into other members with Zn2+ transport functions.
Table 1. X-ray and cryo-EM structure of zinc transporters (ZnTs).
Proteins Main Functions Organisms States Conformations (PDB Code) Ligands Methods References
YiiP Transport Zn2+ out of the cytoplasm and into the periplasm Escherichia coli Homodimer Outward-facing (2QFI, 3H90) Zn2+ X-ray diffraction [41][42]
Shewanella oneidensis Homodimer Inward-facing (3J1Z, 5VRF, 7KZZ (1)) Zn2+ Electron microscopy [44][45][46]
  Homodimer Inward-facing occluded (7KZX) Zn2+ [43]
ZnT7 Transport Zn2+ out of the cytoplasm and into the Golgi lumen Homo sapiens Homodimer Outward-facing (8J7T) Apo Electron microscopy [50]
Homodimer Outward-facing (8J7U) Zn2+
Heterodimer Inward-facing and outward-facing (8J7V (2)) Apo
Heterodimer Inward-facing with Zn2+ and outward-facing (8J80 (3)) Zn2+, Apo
Heterodimer Inward-facing with Zn2+ and outward-facing with Zn2+ (8J7W) (4) Zn2+
ZnT8 Transport Zn2+ out of the cytoplasm and into the insulin secretory granule H. sapiens Homodimer Outward-facing (6XPE) Zn2+ Electron microscopy [51]
Heterodimer Outward-facing and inward-facing (6XPF) Apo
Xenopus tropicalis Homodimer Outward-facing (7Y5G) Zn2+ [52]
Homodimer Outward-facing (7Y5H (5)) Apo
(1) This structure was observed in the presence of 0.5 mM EDTA. (2) This structure was observed in the absence of Zn2+. (3) This structure was observed in the presence of 10 μM Zn2+. (4) This structure was observed with addition of 200 and 300 μM Zn2+. (5) This structure was observed at low pH.

2. Zn2+ Transport Systems in Prokaryotes and Eukaryotes

Prokaryotes and eukaryotes have developed a variety of Zn2+ transport systems to promote the uptake or efflux of Zn2+ across biological membranes. ZnTs can be divided into three major groups depending on the mode of transport: Uniporters that transport Zn2+ alone; symporters that transport Zn2+ in the same direction as other ions, such as protons; and antiporters that transport Zn2+ and another ion in opposite directions, such that the binding of one is concomitant with the release of the other. In general, uniporters require no external energy input and transport specific molecules along their concentration gradients; they are therefore passive transporters. However, it can also act as an active transporter if the transport process is against the concentration gradient. By contrast, symporters and antiporters use the energy stored in the concentration gradient of another ion, in many cases, a proton, to transport specific molecules against their concentration gradients. In this regard, symporters and antiporters can be regarded as active transporters. In addition, some P-ATPases and ABC transporters transport Zn2+ using ATP as an external energy source to overcome the Zn2+ concentration gradient.
Zinc transporters (ZnTs) and ZRT- and IRT-related proteins (ZIPs) are the two major Zn2+ transport families found universally in bacteria, yeasts, plants, and animals, including humans. ZnTs and ZIPs selectively transport Zn2+, but in opposite directions: ZnTs export Zn2+ from the cytoplasm, whereas ZIPs import Zn2+ into the cytoplasm. Thus, ZnTs and ZIPs play important roles in maintaining homeostasis of intracellular and intra-organelle Zn2+ levels.
While ZntB from Escherichia coli (EcZntB) acts as a Zn2+/H+ symporter [53], many ZnTs function as proton-driven antiporters, exchanging H+ in the extracellular space or organelle lumens for Zn2+ in the cytoplasm [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. By contrast, there is no clear evidence that ZIPs use proton energy flux to transport Zn2+ across the membranes. However, recent biochemical studies suggest that, like ZnTs, Bordetella bronchiseptica ZIP (BbZIP) may function as a Zn2+/H+ antiporter [56].

3. ZnTs

ZnTs belong to the cation diffusion facilitator (CDF) family, which can be classified into three groups: Zn-CDFs, Zn/Fe-CDFs, and Mn-CDFs [57][58]. Zn-CDFs consist of Zn2+ and Co2+ transporters, including ZitB-like, ZnT1-like, and Zrc1-like proteins. The ZitB-like clusters are from E. coli. The ZnT1-like clusters include only metazoans. The Zrc1-like cluster includes only fungal CDFs originating from Ascomycetes, Basidiomycetes, and Zygomycetes. Zn/Fe-CDFs are cation-efflux pumps that transport Fe2+ or Zn2+, and also Co2+, Cd2+, and Ni2+. Mn-CDFs include metal tolerance proteins (MTPs) from plants.

3.1. Mammalian ZnTs

Ten ZnTs (ZnTs 1–10) have been identified in mammals, including humans [59][60]. All ZnTs are Zn-CDF members, although ZnT10 is more likely a manganese transporter [59][60][61]. Based on their amino acid sequence similarities, ZnTs are divided into four subgroups: Group 1 includes ZnT5 and ZnT7; group 2 includes ZnT2-ZnT4 and ZnT8; group 3 includes ZnT1 and ZnT10; and group 4 includes ZnT6 and ZnT9 [60]. Most ZnTs form a homodimer composed of the same protomers [50][51][52], whereas ZnT5 and ZnT6 form a heterodimer including two different protomers [62], and all are located on the plasma or organelle membranes, where they control intracellular and extracellular Zn2+ balance [59][63]. Specifically, ZnT7 transports Zn2+ into the lumen of the pre-cis- and cis-Golgi, whereas ZnT5/6 and ZnT4 transport Zn2+ into the lumen of the medial- and trans-Golgi [64]. ZnT7 and ZnT5/6 are responsible for the Golgi-to-ER retrograde transport of the ER chaperone ERp44 [64]. This system is involved in the maturation and activation of some secretory proteins during transport through the early secretory pathway [65].

3.2. Plant ZnTs

Metal tolerance proteins (MTPs) are bivalent cationic transporters in plants that play crucial roles in metal tolerance and homeostasis in metal non-hyperaccumulators (e.g., Arabidopsis thaliana) and hyperaccumulators (e.g., Arabidopsis halleri and Noccaea caerulescens) [66]. MTPs are classified into seven groups based on their amino acid sequence similarities [67]. Thus, plant MTPs are very diverse so as to satisfy the need to absorb or detoxify specific metals. A. thalaina has 12 MTPs, while P. trichocarpa MTP has up to 22 MTP genes [68]. In A. thaliana, AtMTP1 and AtMTP3 ZnTs localized on the vacuole membrane maintain Zn2+ homeostasis [69][70][71]. AtMTP1 and AtMTP3 are involved in the sequestration of excess cytoplasmic Zn2+ into vacuoles [71]. Whereas AtMTP1 is more ubiquitously expressed, expression of AtMTP3 is restricted to the root epidermis and cortex [69][72]. Like mammalian ZnT5 and ZnT6, AtMTP5 and AtMTP12 form a heterodimer at the Golgi membrane and transport Zn2+ into the Golgi lumen [73].

3.3. Yeast ZnTs

Researchers'understanding of ZnTs in yeast derives primarily from Saccharomyces cerevisiae. In S. cerevisiae, vacuolar ZnTs ZRC1 and COT1 act as Zn2+/H+ antiporters and regulate Zn2+ homeostasis by transporting and storing Zn2+ in the vacuole [74][75]. ScZRC1 senses Zn2+ availability in the cytosol, possibly through the histidine-repeat motifs, and transports Zn2+ from the cytosol to the vacuole when cytosolic Zn2+ is abundant, thereby conferring resistance to Zn2+ toxicity [76][77].
S. cerevisiae also possesses Msc2 and Zrg17, which transport Zn2+ from the nucleus and ER to the cytoplasm [78]. ScMsc2 and ScZrg17 interact physically to form a heterodimer and likely serve to maintain the Zn2+ levels in the ER of Zn2+-adequate cells [79][80][81]. Schizosaccharomyces pombe also has a zinc transporter, called ZHF1, which maintains Zn2+ homeostasis in the ER and nucleus and sequesters Cd2+ into the ER [82]. The structures of yeast ZnTs have not yet been reported. While ScZRC1, ScCOT1, and ScZrg17 are predicted to have six transmembrane (TM) helices, ScMsc2 is presumed to contain up to 16 TM helices.

3.4. Bacterial ZnTs

Bacterial ZnTs YiiP, ZitB, and CzcD have been functionally characterized. Insight into the structural features and Zn2+ transport mechanisms of bacterial ZnTs comes primarily from YiiP. YiiP was first identified in Escherichia coli [83]. In vitro, YiiP also binds Hg2+, Co2+, Ni2+, Mn2+, Ca2+, and Mg2+ but is unlikely to transport them efficiently [84]. Like mammalian ZnTs, YiiP functions as a Zn2+/H+ antiporter [43][48].
Other ZnTs have been identified recently in bacteria. ZitB conducts Zn2+ efflux across the cytoplasmic membrane, thereby reducing Zn2+ accumulation in the cytoplasm and rendering bacteria more resistant to Zn2+ [85]. By contrast, ZntA, a Zn2+-transporting P-ATPase, is required for growth at more toxic concentrations [85]. CzcD is a Cd2+, Co2+, and Zn2+/H+-K+ antiporter involved in maintaining intracellular divalent cation and potassium homeostasis through active efflux of Zn2+, Cd2+, and Co2+ in exchange for K+ and protons [86].

References

  1. Skalny, A.V.; Aschner, M.; Tinkov, A.A. Zinc. Adv. Food Nutr. Res. 2021, 96, 251–310.
  2. Zaher, D.M.; El-Gamal, M.I.; Omar, H.A.; Aljareh, S.N.; Al-Shamma, S.A.; Ali, A.J.; Zaib, S.; Iqbal, J. Recent advances with alkaline phosphatase isoenzymes and their inhibitors. Arch. Pharm. 2020, 353, e2000011.
  3. Xiong, L.; Peng, M.; Zhao, M.; Liang, Z. Truncated expression of a Carboxypeptidase A from bovine improves its enzymatic properties and detoxification efficiency of Ochratoxin A. Toxins 2020, 12, 680.
  4. Luan, R.; Ding, D.; Xue, Q.; Li, H.; Wang, Y.; Yang, J. Protective role of zinc in the pathogenesis of respiratory diseases. Eur. J. Clin. Nutr. 2023, 77, 427–435.
  5. Begum, F.; Me, H.M.; Christov, M. The role of zinc in cardiovascular disease. Cardiol. Rev. 2022, 30, 100–108.
  6. Gembillo, G.; Visconti, L.; Giuffrida, A.E.; Labbozzetta, V.; Peritore, L.; Lipari, A.; Calabrese, V.; Piccoli, G.B.; Torreggiani, M.; Siligato, R.; et al. Role of zinc in diabetic kidney disease. Nutrients 2022, 14, 1353.
  7. Li, J.; Cao, D.; Huang, Y.; Chen, B.; Chen, Z.; Wang, R.; Dong, Q.; Wei, Q.; Liu, L. Zinc intakes and health outcomes: An umbrella review. Front. Nutr. 2022, 9, 798078.
  8. Li, Z.; Liu, Y.; Wei, R.; Yong, V.W.; Xue, M. The important role of zinc in neurological diseases. Biomolecules 2022, 13, 28.
  9. Garner, T.B.; Hester, J.M.; Carothers, A.; Diaz, F.J. Role of zinc in female reproduction. Biol. Reprod. 2021, 104, 976–994.
  10. Banupriya, N.; Bhat, B.V.; Sridhar, M.G. Role of zinc in neonatal sepsis. Indian J. Pediatr. 2021, 88, 696–702.
  11. Tamura, Y. The role of zinc homeostasis in the prevention of diabetes mellitus and cardiovascular diseases. J. Atheroscler. Thromb. 2021, 28, 1109–1122.
  12. Allouche-Fitoussi, D.; Breitbart, H. The role of zinc in male fertility. Int. J. Mol. Sci. 2020, 21, 7796.
  13. Michalczyk, K.; Cymbaluk-Płoska, A. The role of zinc and copper in gynecological malignancies. Nutrients 2020, 12, 3732.
  14. Granero, R.; Pardo-Garrido, A.; Carpio-Toro, I.L.; Ramírez-Coronel, A.A.; Martínez-Suárez, P.C.; Reivan-Ortiz, G.G. The role of iron and zinc in the treatment of ADHD among children and adolescents: A systematic review of randomized clinical trials. Nutrients 2021, 13, 4059.
  15. Moshtagh, M.; Amiri, R. Role of zinc supplementation in the improvement of acute respiratory infections among Iranian children: A systematic review. Tanaffos 2020, 19, 1–9.
  16. Wang, M.X.; Win, S.S.; Pang, J. Zinc supplementation reduces common cold duration among healthy adults: A systematic review of randomized controlled trials with micronutrients supplementation. Am. J. Trop. Med. Hyg. 2020, 103, 86–99.
  17. Korkmaz-Icöz, S.; Atmanli, A.; Radovits, T.; Li, S.; Hegedüs, P.; Ruppert, M.; Brlecic, P.; Yoshikawa, Y.; Yasui, H.; Karck, M.; et al. Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes. J. Physiol. Sci. 2016, 66, 113–125.
  18. Barnett, J.B.; Dao, M.C.; Hamer, D.H.; Kandel, R.; Brandeis, G.; Wu, D.; Dallal, G.E.; Jacques, P.F.; Schreiber, R.; Kong, E.; et al. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: A randomized, double-blind, placebo-controlled trial. Am. J. Clin. Nutr. 2016, 103, 942–951.
  19. Cope, E.C.; Levenson, C.W. Role of zinc in the development and treatment of mood disorders. Curr. Opin. Clin. Nutr. Metab. Care 2010, 13, 685–689.
  20. Plum, L.M.; Rink, L.; Haase, H. The essential toxin: Impact of zinc on human health. Int. J. Environ. Res. Public Health 2010, 7, 1342–1365.
  21. Fox, M.R.S. Zinc Excess. In Zinc in Human Biology. ILSI Human Nutrition Reviews; Mills, C.F., Ed.; Springer: London, UK, 1989; pp. 365–370.
  22. Brown, M.A.; Thom, J.V.; Orth, G.L.; Cova, P.; Juarez, J. Food poisoning involving zinc contamination. Arch. Environ. Health 1964, 8, 657–660.
  23. Skalny, A.V.; Aschner, M.; Lei, X.G.; Gritsenko, V.A.; Santamaria, A.; Alekseenko, S.I.; Prakash, N.T.; Chang, J.S.; Sizova, E.A.; Chao, J.C.J.; et al. Gut Microbiota as a Mediator of Essential and Toxic Effects of Zinc in the Intestines and Other Tissues. Int. J. Mol. Sci. 2021, 22, 13074.
  24. Hamzah-Saleem, M.; Usman, K.; Rizwan, M.; Al-Jabri, H.; Alsafran, M. Functions and strategies for enhancing zinc availability in plants for sustainable agriculture. Front. Plant Sci. 2022, 13, 1033092.
  25. Choudhury, R.; Srivastava, S. Zinc resistance mechanisms in bacteria. Curr. Sci. 2001, 81, 768–775.
  26. Pandey, N.; Pathak, G.C.; Sharma, C.P. Zinc is critically required for pollen function and fertilisation in lentil. J. Trace Elem. Med. Biol. 2006, 20, 89–96.
  27. Wissuwa, M.; Ismail, A.M.; Yanagihara, S. Effects of zinc deficiency on rice growth and genetic factors contributing to tolerance. Plant Physiol. 2006, 142, 731–741.
  28. Corbett, D.; Wang, J.; Schuler, S.; Lopez-Castejon, G.; Glenn, S.; Brough, D.; Andrew, P.W.; Cavet, J.S.; Roberts, I.S. Two zinc uptake systems contribute to the full virulence of Listeria monocytogenes during growth in vitro and in vivo. Infect. Immun. 2012, 80, 14–21.
  29. Hara, T.; Yoshigai, E.; Ohashi, T.; Fukada, T. Zinc transporters as potential therapeutic targets: An updated review. J. Pharmacol. Sci. 2022, 148, 221–228.
  30. Zhu, B.; Huo, R.; Zhi, Q.; Zhan, M.; Chen, X.; Hua, Z.C. Increased expression of zinc transporter ZIP4, ZIP11, ZnT1, and ZnT6 predicts poor prognosis in pancreatic cancer. J. Trace Elem. Med. Biol. 2021, 65, 126734.
  31. Lei, P.; Ayton, S.; Bush, A.I. The essential elements of Alzheimer’s disease. J. Biol. Chem. 2021, 296, 100105.
  32. Xu, Y.; Xiao, G.; Liu, L.; Lang, M. Zinc transporters in Alzheimer’s disease. Mol. Brain 2019, 12, 106.
  33. Sikora, J.; Ouagazzal, A.M. Synaptic zinc: An emerging player in Parkinson’s disease. Int. J. Mol. Sci. 2021, 22, 4724.
  34. Davis, D.N.; Strong, M.D.; Chambers, E.; Hart, M.D.; Bettaieb, A.; Clarke, S.L.; Smith, B.J.; Stoecker, B.J.; Lucas, E.A.; Lin, D.; et al. A role for zinc transporter gene SLC39A12 in the nervous system and beyond. Gene 2021, 799, 145824.
  35. Chowanadisai, W.; Lönnerdal, B.; Kelleher, S.L. Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. J. Biol. Chem. 2006, 281, 39699–39707.
  36. Lieberwirth, J.K.; Joset, P.; Heinze, A.; Hentschel, J.; Stein, A.; Iannaccone, A.; Steindl, K.; Kuechler, A.; Abou-Jamra, R. Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy. Eur. J. Hum. Genet. 2021, 29, 808–815.
  37. Hildebrand, M.S.; Phillips, A.M.; Mullen, S.A.; Adlard, P.A.; Hardies, K.; Damiano, J.A.; Wimmer, V.; Bellows, S.T.; McMahon, J.M.; Burgess, R.; et al. Loss of synaptic Zn2+ transporter function increases risk of febrile seizures. Sci. Rep. 2015, 5, 17816.
  38. Pérez, Y.; Shorer, Z.; Liani-Leibson, K.; Chabosseau, P.; Kadir, R.; Volodarsky, M.; Halperin, D.; Barber-Zucker, S.; Shalev, H.; Schreiber, R.; et al. SLC30A9 mutation affecting intracellular zinc homeostasis causes a novel cerebro-renal syndrome. Brain 2017, 140, 928–939.
  39. Tavasoli, A.; Arjmandi-Rafsanjani, K.; Hemmati, S.; Mojbafan, M.; Zarei, E.; Hosseini, S. A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: A treatable inborn error of manganese metabolism. BMC Pediatr. 2019, 19, 229.
  40. Quadri, M.; Federico, A.; Zhao, T.; Breedveld, G.J.; Battisti, C.; Delnooz, C.; Severijnen, L.A.; Di Toro Mammarella, L.; Mignarri, A.; Monti, L.; et al. Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease. Am. J. Hum. Genet. 2012, 90, 467–477.
  41. Lu, M.; Fu, D. Structure of the zinc transporter YiiP. Science 2007, 317, 1746–1748.
  42. Lu, M.; Chai, J.; Fu, D. Structural basis for autoregulation of the zinc transporter YiiP. Nat. Struct. Mol. Biol. 2009, 16, 1063–1067.
  43. Hussein, A.; Fan, S.; Lopez-Redondo, M.L.; Kenney, I.; Zhang, X.; Beckstein, O.; Stokes, D.L. Energy coupling and stoichiometry of Zn2+/H+ antiport by the cation diffusion facilitator YiiP. eLife 2023, 12, RP87167.
  44. Lopez-Redondo, M.L.; Fan, S.; Koide, A.; Koide, S.; Beckstein, O.; Stokes, D.L. Zinc binding alters the conformational dynamics and drives the transport cycle of the cation diffusion facilitator YiiP. J. Gen. Physiol. 2021, 153, e202112873.
  45. Lopez-Redondo, M.L.; Coudray, N.; Zhang, Z.; Alexopoulos, J.; Stokes, D.L. Structural basis for the alternating access mechanism of the cation diffusion facilitator YiiP. Proc. Natl. Acad. Sci. USA 2018, 115, 3042–3047.
  46. Coudray, N.; Valvo, S.; Hu, M.; Lasala, R.; Kim, C.; Vink, M.; Zhou, M.; Provasi, D.; Filizola, M.; Tao, J.; et al. Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy. Proc. Natl. Acad. Sci. USA 2013, 110, 2140–2145.
  47. Chao, Y.; Fu, D. Kinetic study of the antiport mechanism of an Escherichia coli zinc transporter, ZitB. J. Biol. Chem. 2004, 279, 12043–12050.
  48. Chao, Y.; Fu, D. Thermodynamic studies of the mechanism of metal binding to the Escherichia coli zinc transporter YiiP. J. Biol. Chem. 2004, 279, 17173–17180.
  49. Sharma, G.; Merz, K.M. Mechanism of zinc transport through the zinc transporter YiiP. J. Chem. Theory Comput. 2022, 18, 2556–2568.
  50. Bui, H.B.; Watanabe, S.; Nomura, N.; Liu, K.; Uemura, T.; Inoue, M.; Tsutsumi, A.; Fujita, H.; Kinoshita, K.; Kato, Y.; et al. Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus. Nat. Commun. 2023, 14, 4770.
  51. Xue, J.; Xie, T.; Zeng, W.; Jiang, Y.; Bai, X.C. Cryo-EM structures of human ZnT8 in both outward- and inward-facing conformations. eLife 2020, 9, e58823.
  52. Zhang, S.; Fu, C.; Luo, Y.; Xie, Q.; Xu, T.; Sun, Z.; Su, Z.; Zhou, X. Cryo-EM structure of a eukaryotic zinc transporter at a low pH suggests its Zn2+-releasing mechanism. J. Struct. Biol. 2023, 215, 107926.
  53. Gati, C.; Stetsenko, A.; Slotboom, D.J.; Scheres, S.H.W.; Guskov, A. The structural basis of proton driven zinc transport by ZntB. Nat. Commun. 2017, 8, 1313.
  54. Golan, Y.; Alhadeff, R.; Warshel, A.; Assaraf, Y.G. ZnT2 is an electroneutral proton-coupled vesicular antiporter displaying an apparent stoichiometry of two protons per zinc ion. PLoS Comput. Biol. 2019, 15, e1006882.
  55. Cotrim, C.A.; Jarrott, R.J.; Martin, J.L.; Drew, D. A structural overview of the zinc transporters in the cation diffusion facilitator family. Acta Crystallogr. D Struct. Biol. 2019, 75, 357–367.
  56. Pang, C.; Chai, J.; Zhu, P.; Shanklin, J.; Liu, Q. Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters. Nat. Commun. 2023, 14, 3404.
  57. Montanini, B.; Blaudez, D.; Jeandroz, S.; Sanders, D.; Chalot, M. Phylogenetic and functional analysis of the Cation Diffusion Facilitator (CDF) family: Improved signature and prediction of substrate specificity. BMC Genom. 2007, 8, 107.
  58. Gaither, L.A.; Eide, D.J. Eukaryotic zinc transporters and their regulation. Biometals 2001, 14, 251–270.
  59. Kambe, T.; Taylor, K.M.; Fu, D. Zinc transporters and their functional integration in mammalian cells. J. Biol. Chem. 2021, 296, 100320.
  60. Kambe, T.; Tsuji, T.; Hashimoto, A.; Itsumura, N. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol. Rev. 2015, 95, 749–784.
  61. Hara, T.; Takeda, T.A.; Takagishi, T.; Fukue, K.; Kambe, T.; Fukada, T. Physiological roles of zinc transporters: Molecular and genetic importance in zinc homeostasis. J. Physiol. Sci. 2017, 67, 283–301.
  62. Fukunaka, A.; Suzuki, T.; Kurokawa, Y.; Yamazaki, T.; Fujiwara, N.; Ishihara, K.; Migaki, H.; Okumura, K.; Masuda, S.; Yamaguchi-Iwai, Y.; et al. Demonstration and characterization of the heterodimerization of ZnT5 and ZnT6 in the early secretory pathway. J. Biol. Chem. 2009, 284, 30798–30806.
  63. Huang, L.; Tepaamorndech, S. The SLC30 family of zinc transporters: A review of current understanding of their biological and pathophysiological roles. Mol. Asp. Med. 2013, 34, 548–560.
  64. Amagai, Y.; Yamada, M.; Kowada, T.; Watanabe, T.; Du, Y.; Liu, R.; Naramoto, S.; Watanabe, S.; Kyozuka, J.; Anelli, T.; et al. Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface. Nat. Commun. 2023, 14, 2683.
  65. Kambe, T.; Wagatsuma, T. Metalation and activation of Zn2+ enzymes via early secretory pathway-resident ZNT proteins. Biophys. Rev. 2023, 4, 041302.
  66. Ricachenevsky, F.K.; Menguer, P.K.; Sperotto, R.A.; Williams, L.E.; Fett, J.P. Roles of plant metal tolerance proteins (MTP) in metal storage and potential use in biofortification strategies. Front. Plant Sci. 2013, 4, 144.
  67. Gustin, J.L.; Zanis, M.J.; Salt, D.E. Structure and evolution of the plant cation diffusion facilitator family of ion transporters. BMC Evol. Biol. 2011, 11, 76.
  68. Gao, Y.; Yang, F.; Liu, J.; Xie, W.; Zhang, L.; Chen, Z.; Peng, Z.; Ou, Y.; Yao, Y. Genome-wide identification of metal tolerance protein genes in Populus trichocarpa and their roles in response to various heavy metal stresses. Int. J. Mol. Sci. 2020, 21, 1680.
  69. Arrivault, S.; Senger, T.; Krämer, U. The Arabidopsis metal tolerance protein AtMTP3 maintains metal homeostasis by mediating Zn exclusion from the shoot under Fe deficiency and Zn oversupply. Plant J. 2006, 46, 861–879.
  70. Desbrosses-Fonrouge, A.G.; Voigt, K.; Schröder, A.; Arrivault, S.; Thomine, S.; Krämer, U. Arabidopsis thaliana MTP1 is a Zn transporter in the vacuolar membrane which mediates Zn detoxification and drives leaf Zn accumulation. FEBS Lett. 2005, 579, 4165–4174.
  71. Kobae, Y.; Uemura, T.; Sato, M.H.; Ohnishi, M.; Mimura, T.; Nakagawa, T.; Maeshima, M. Zinc transporter of Arabidopsis thaliana AtMTP1 is localized to vacuolar membranes and implicated in zinc homeostasis. Plant Cell Physiol. 2004, 45, 1749–1758.
  72. Sinclair, S.A.; Krämer, U. The zinc homeostasis network of land plants. Biochim. Biophys. Acta 2012, 1823, 1553–1567.
  73. Fujiwara, T.; Kawachi, M.; Sato, Y.; Mori, H.; Kutsuna, N.; Hasezawa, S.; Maeshima, M. A high molecular mass zinc transporter MTP12 forms a functional heteromeric complex with MTP5 in the Golgi in Arabidopsis thaliana. FEBS J. 2015, 282, 1965–1979.
  74. Miyabe, S.; Izawa, S.; Inoue, Y. The Zrc1 is involved in zinc transport system between vacuole and cytosol in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 2001, 282, 79–83.
  75. MacDiarmid, C.W.; Milanick, M.A.; Eide, D.J. Biochemical properties of vacuolar zinc transport systems of Saccharomyces cerevisiae. J. Biol. Chem. 2002, 277, 39187–39194.
  76. MacDiarmid, C.W.; Milanick, M.A.; Eide, D.J. Induction of the ZRC1 metal tolerance gene in zinc-limited yeast confers resistance to zinc shock. J. Biol. Chem. 2003, 278, 15065–15072.
  77. Lin, H.; Kumánovics, A.; Nelson, J.M.; Warner, D.E.; Ward, D.M.; Kaplan, J. A single amino acid change in the yeast vacuolar metal transporters ZRC1 and COT1 alters their substrate specificity. J. Biol. Chem. 2008, 283, 33865–33873.
  78. Li, L.; Kaplan, J. The yeast gene MSC2, a member of the cation diffusion facilitator family, affects the cellular distribution of zinc. J. Biol. Chem. 2001, 276, 5036–5043.
  79. Wu, Y.H.; Taggart, J.; Song, P.X.; MacDiarmid, C.; Eide, D.J. An MSC2 promoter-lacZ fusion gene reveals zinc-responsive changes in sites of transcription initiation that occur across the yeast genome. PLoS ONE 2016, 11, e0163256.
  80. Ellis, C.D.; Macdiarmid, C.W.; Eide, D.J. Heteromeric protein complexes mediate zinc transport into the secretory pathway of eukaryotic cells. J. Biol. Chem. 2005, 280, 28811–28818.
  81. Ellis, C.D.; Wang, F.; MacDiarmid, C.W.; Clark, S.; Lyons, T.; Eide, D.J. Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function. J. Cell Biol. 2004, 166, 325–335.
  82. Clemens, S.; Bloss, T.; Vess, C.; Neumann, D.; Nies, D.H.; Zur Nieden, U. A transporter in the endoplasmic reticulum of Schizosaccharomyces pombe cells mediates zinc storage and differentially affects transition metal tolerance. J. Biol. Chem. 2002, 277, 18215–18221.
  83. Grass, G.; Otto, M.; Fricke, B.; Haney, C.J.; Rensing, C.; Nies, D.H.; Munkelt, D. FieF (YiiP) from Escherichia coli mediates decreased cellular accumulation of iron and relieves iron stress. Arch. Microbiol. 2005, 183, 9–18.
  84. Wei, Y.; Fu, D. Selective metal binding to a membrane-embedded aspartate in the Escherichia coli metal transporter YiiP (FieF). J. Biol. Chem. 2005, 280, 33716–33724.
  85. Grass, G.; Fan, B.; Rosen, B.P.; Franke, S.; Nies, D.H.; Rensing, C. ZitB (YbgR), a member of the cation diffusion facilitator family, is an additional zinc transporter in Escherichia coli. J. Bacteriol. 2001, 183, 4664–4667.
  86. Guffanti, A.A.; Wei, Y.; Rood, S.V.; Krulwich, T.A. An antiport mechanism for a member of the cation diffusion facilitator family: Divalent cations efflux in exchange for K+ and H+. Mol. Microbiol. 2002, 45, 145–153.
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Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Han Ba Bui
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Kenji Inaba
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Update Date: 12 Mar 2024
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