Structures of AAA protein translocase Bcs1 suggest translocation mechanism of a folded protein.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Tang, WK; Borgnia, MJ; Hsu, AL; Esser, L; Fox, T; de Val, N; Xia, D

Published Date

  • February 2020

Published In

Volume / Issue

  • 27 / 2

Start / End Page

  • 202 - 209

PubMed ID

  • 32042153

Pubmed Central ID

  • PMC8482623

Electronic International Standard Serial Number (EISSN)

  • 1545-9985

Digital Object Identifier (DOI)

  • 10.1038/s41594-020-0373-0

Language

  • eng

Conference Location

  • United States