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The two-domain elev...
The two-domain elevator-type mechanism of zinc-transporting ZIP proteins
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- Wiuf, Anders (författare)
- Department of Biomedical Sciences, University of Copenhagen, Mærsk Tower 7-9, Nørre Allé 14, Copenhagen, Denmark
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- Steffen, Jonas Hyld (författare)
- Department of Biomedical Sciences, University of Copenhagen, Mærsk Tower 7-9, Nørre Allé 14, Copenhagen, Denmark
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- Becares, Eva Ramos (författare)
- Department of Biomedical Sciences, University of Copenhagen, Mærsk Tower 7-9, Nørre Allé 14, Copenhagen, Denmark
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- Grønberg, Christina (författare)
- Department of Biomedical Sciences, University of Copenhagen, Mærsk Tower 7-9, Nørre Allé 14, Copenhagen, Denmark
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- Mahato, Dhani Ram (författare)
- Umeå University,Umeå universitet,Kemiska institutionen
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- Rasmussen, Søren G.F. (författare)
- Department of Neuroscience, University of Copenhagen, Maersk Tower 7-5, Nørre Allé 14, Copenhagen, Denmark
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- Andersson, Magnus (författare)
- Umeå University,Umeå universitet,Kemiska institutionen
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- Croll, Tristan (författare)
- Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Keith Peters Building, Hills Rd., Cambridge, United Kingdom
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- Gotfryd, Kamil (författare)
- Department of Biomedical Sciences, University of Copenhagen, Mærsk Tower 7-9, Nørre Allé 14, Copenhagen, Denmark
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- Gourdon, Pontus (författare)
- Lund University,Lunds universitet,Membranproteinstrukturbiologi,Forskargrupper vid Lunds universitet,Membrane Protein Structural Biology,Lund University Research Groups,University of Copenhagen
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(creator_code:org_t)
- American Association for the Advancement of Science, 2022
- 2022
- Engelska.
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Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 8:28
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
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Wiuf, Anders
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Steffen, Jonas H ...
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Becares, Eva Ram ...
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Grønberg, Christ ...
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Mahato, Dhani Ra ...
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Rasmussen, Søren ...
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visa fler...
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Andersson, Magnu ...
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Croll, Tristan
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Gotfryd, Kamil
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Gourdon, Pontus
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- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Strukturbiologi
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Science Advances
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Umeå universitet
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Lunds universitet