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TitleStructural insights into the calcium-coupled zinc export of human ZnT1.
Journal, issue, pagesSci Adv, Vol. 10, Issue 17, Page eadk5128, Year 2024
Publish dateApr 26, 2024
AuthorsChunqiao Sun / Bangguo He / Yongxiang Gao / Xingbing Wang / Xin Liu / Linfeng Sun /
PubMed AbstractCellular zinc (Zn) homeostasis is essential to human health and is under tight regulations. Human zinc transporter 1 (hZnT1) is a plasma membrane-localized Zn exporter belonging to the ZnT family, ...Cellular zinc (Zn) homeostasis is essential to human health and is under tight regulations. Human zinc transporter 1 (hZnT1) is a plasma membrane-localized Zn exporter belonging to the ZnT family, and its functional aberration is associated with multiple diseases. Here, we show that hZnT1 works as a Zn/Ca exchanger. We determine the structure of hZnT1 using cryo-electron microscopy (cryo-EM) single particle analysis. hZnT1 adopts a homodimeric structure, and each subunit contains a transmembrane domain consisting of six transmembrane segments, a cytosolic domain, and an extracellular domain. The transmembrane region displays an outward-facing conformation. On the basis of structural and functional analysis, we propose a model for the hZnT1-mediated Zn/Ca exchange. Together, these results facilitate our understanding of the biological functions of hZnT1 and provide a basis for further investigations of the ZnT family transporters.
External linksSci Adv / PubMed:38669333 / PubMed Central
MethodsEM (single particle)
Resolution3.4 Å
Structure data

35949

8j2g

EMDB-35949, PDB-8j2g:
Human ZnT1-D47N/D255N mutant
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / zinc exporter

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