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| Title | Conformations of Bcs1L undergoing ATP hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate. |
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| Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 4655, Year 2024 |
| Publish date | May 31, 2024 |
 Authors | Jingyu Zhan / Allison Zeher / Rick Huang / Wai Kwan Tang / Lisa M Jenkins / Di Xia /  |
| PubMed 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 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. |
 External links | Nat Commun / PubMed:38821922 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.02 - 7.2 Å |
| Structure data | EMDB-40954, PDB-8t14: EMDB-41061, PDB-8t5u: EMDB-41095, PDB-8t7u: EMDB-41148, PDB-8tby: EMDB-41276, PDB-8ti0: EMDB-41462, PDB-8tp1: EMDB-41476, PDB-8tpl:  EMDB-41609: Bcs1 bound with ISP-ED |
| Chemicals |  ChemComp-ADP:  ChemComp-MG:  ChemComp-ATP: |
| Source |
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 Keywords | TRANSLOCASE / Heptamer / AAA-ATPase / ADP-bound / ATP-bound |
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