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Diverse roles of th...
Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases
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- Guo, Zongxin (författare)
- Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark
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- Orädd, Fredrik, 1994- (författare)
- Umeå University,Umeå universitet,Kemiska institutionen
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- Bågenholm, Viktoria (författare)
- Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark
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- Grønberg, Christina (författare)
- Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark
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- Ma, Jian Feng (författare)
- Institute of Plant Science and Resources, Okayama University, Japan
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- Ott, Peter (författare)
- Medical Department of Hepatology and Gastroenterology, Aarhus University Hospital, Skejby, Denmark
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- Wang, Yong (författare)
- College of Life Sciences, Zhejiang University, Zhejiang, China
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- Andersson, Magnus (författare)
- Umeå University,Umeå universitet,Kemiska institutionen
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- Amstrup Pedersen, Per (författare)
- Department of Biology, University of Copenhagen, Copenhagen, Denmark
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- Wang, Kaituo (författare)
- Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark,Institute of Botany, Chinese Academy of Sciences
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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)
- Springer Nature, 2024
- 2024
- Engelska.
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15
- 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
- Copper transporting P-type (P1B-1-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P1B-1-ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P1B-1-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD−1, serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD−1, MBD−2, likely assists in copper delivery to the ATPase core. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, allowing for copper uptake, binding and release. As such, our findings unify previously conflicting data on the transport and regulation of P1B-1-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P1B-1-disorders and ongoing clinical trials.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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Guo, Zongxin
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Orädd, Fredrik, ...
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Bågenholm, Vikto ...
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Grønberg, Christ ...
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Ma, Jian Feng
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Ott, Peter
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Wang, Yong
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Andersson, Magnu ...
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Amstrup Pedersen ...
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Wang, Kaituo
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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 Biofysik
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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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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
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Nature Communica ...
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Umeå universitet
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