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Conformations of Bcs1L undergoing ATP hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate.
- Source :
-
Nature communications [Nat Commun] 2024 May 31; Vol. 15 (1), pp. 4655. Date of Electronic Publication: 2024 May 31. - Publication Year :
- 2024
-
Abstract
- The human AAA-ATPase Bcs1L translocates the fully assembled Rieske iron-sulfur protein (ISP) precursor across the mitochondrial inner membrane, enabling respiratory Complex III assembly. Exactly how the folded substrate is bound to and released from Bcs1L has been unclear, and there has been ongoing debate as to whether subunits of Bcs1L act in sequence or in unison hydrolyzing ATP when moving the protein cargo. Here, we captured Bcs1L conformations by cryo-EM during active ATP hydrolysis in the presence or absence of ISP substrate. In contrast to the threading mechanism widely employed by AAA proteins in substrate translocation, subunits of Bcs1L alternate uniformly between ATP and ADP conformations without detectable intermediates that have different, co-existing nucleotide states, indicating that the subunits act in concert. We further show that the ISP can be trapped by Bcs1 when its subunits are all in the ADP-bound state, which we propose to be released in the apo form.<br /> (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Subjects :
- Humans
Adenosine Diphosphate metabolism
Adenosine Triphosphate metabolism
Cryoelectron Microscopy
Hydrolysis
Iron-Sulfur Proteins metabolism
Iron-Sulfur Proteins chemistry
Models, Molecular
Protein Conformation
Protein Folding
Protein Transport
ATPases Associated with Diverse Cellular Activities metabolism
ATPases Associated with Diverse Cellular Activities chemistry
Electron Transport Complex III metabolism
Electron Transport Complex III chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 38821922
- Full Text :
- https://doi.org/10.1038/s41467-024-49029-y