7z6m

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Crystal structure of Zn2+-transporter BbZIP in a cadmium bound stateCrystal structure of Zn2+-transporter BbZIP in a cadmium bound state

Structural highlights

7z6m is a 1 chain structure with sequence from Bordetella bronchiseptica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.51Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0H3LM39_BORBR

Publication Abstract from PubMed

Zinc is essential for all organisms and yet detrimental at elevated levels. Hence, homeostasis of this metal is tightly regulated. The Zrt/Irt-like proteins (ZIPs) represent the only zinc importers in metazoans. Mutations in human ZIPs cause serious disorders, but the mechanism by which ZIPs transfer zinc remains elusive. Hitherto, structural information is only available for a model member, BbZIP, and as a single, ion-bound conformation, precluding mechanistic insights. Here, we elucidate an inward-open metal-free BbZIP structure, differing substantially in the relative positions of the two separate domains of ZIPs. With accompanying coevolutional analyses, mutagenesis, and uptake assays, the data point to an elevator-type transport mechanism, likely shared within the ZIP family, unifying earlier functional data. Moreover, the structure reveals a previously unknown ninth transmembrane segment that is important for activity in vivo. Our findings outline the mechanistic principles governing ZIP-protein transport and enhance the molecular understanding of ZIP-related disorders.

The two-domain elevator-type mechanism of zinc-transporting ZIP proteins.,Wiuf A, Steffen JH, Becares ER, Gronberg C, Mahato DR, Rasmussen SGF, Andersson M, Croll T, Gotfryd K, Gourdon P Sci Adv. 2022 Jul 15;8(28):eabn4331. doi: 10.1126/sciadv.abn4331. Epub 2022 Jul, 13. PMID:35857505[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Wiuf A, Steffen JH, Becares ER, Grønberg C, Mahato DR, Rasmussen SGF, Andersson M, Croll T, Gotfryd K, Gourdon P. The two-domain elevator-type mechanism of zinc-transporting ZIP proteins. Sci Adv. 2022 Jul 15;8(28):eabn4331. PMID:35857505 doi:10.1126/sciadv.abn4331

7z6m, resolution 2.51Å

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OCA