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TitleStructures of AAA protein translocase Bcs1 suggest translocation mechanism of a folded protein.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 2, Page 202-209, Year 2020
Publish dateFeb 10, 2020
AuthorsWai Kwan Tang / Mario J Borgnia / Allen L Hsu / Lothar Esser / Tara Fox / Natalia de Val / Di Xia /
PubMed AbstractThe mitochondrial membrane-bound AAA protein Bcs1 translocate substrates across the mitochondrial inner membrane without previous unfolding. One substrate of Bcs1 is the iron-sulfur protein (ISP), a ...The mitochondrial membrane-bound AAA protein Bcs1 translocate substrates across the mitochondrial inner membrane without previous unfolding. One substrate of Bcs1 is the iron-sulfur protein (ISP), a subunit of the respiratory Complex III. How Bcs1 translocates ISP across the membrane is unknown. Here we report structures of mouse Bcs1 in two different conformations, representing three nucleotide states. The apo and ADP-bound structures reveal a homo-heptamer and show a large putative substrate-binding cavity accessible to the matrix space. ATP binding drives a contraction of the cavity by concerted motion of the ATPase domains, which could push substrate across the membrane. Our findings shed light on the potential mechanism of translocating folded proteins across a membrane, offer insights into the assembly process of Complex III and allow mapping of human disease-associated mutations onto the Bcs1 structure.
External linksNat Struct Mol Biol / PubMed:32042153 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.17 - 4.4 Å
Structure data

20808

6ukp

EMDB-20808, PDB-6ukp:
Apo mBcs1
Method: EM (single particle) / Resolution: 3.81 Å

20811

6uks

EMDB-20811, PDB-6uks:
ATPgammaS bound mBcs1
Method: EM (single particle) / Resolution: 3.2 Å

PDB-6u1y:
bcs1 AAA domain
Method: X-RAY DIFFRACTION / Resolution: 2.17 Å

PDB-6uko:
Structure analysis of full-length mouse bcs1 complex
Method: X-RAY DIFFRACTION / Resolution: 4.4 Å

Chemicals

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

Source
  • mus musculus (house mouse)
KeywordsHYDROLASE / bcs1 / AAA ATPase / CHAPERONE / Rieske / cytochrome bc1 / AAA ATPases / mitochondrial inner membrane

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