Structure of the Bcs1 AAA-ATPase suggests an airlock-like translocation mechanism for folded proteins

Lukas Kater; Nikola Wagener; Otto Berninghausen; Thomas Becker; Walter Neupert; Roland Beckmann

doi:10.1038/s41594-019-0364-1

Structure of the Bcs1 AAA-ATPase suggests an airlock-like translocation mechanism for folded proteins

Nat Struct Mol Biol. 2020 Feb;27(2):142-149. doi: 10.1038/s41594-019-0364-1. Epub 2020 Jan 27.

Authors

Lukas Kater¹, Nikola Wagener², Otto Berninghausen¹, Thomas Becker¹, Walter Neupert³, Roland Beckmann⁴

Affiliations

¹ Gene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany.
² Department of Biology, University of Munich, Munich, Germany.
³ Biomedical Center, University of Munich, Munich, Germany.
⁴ Gene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, University of Munich, Munich, Germany. beckmann@genzentrum.lmu.de.

PMID: 31988523
DOI: 10.1038/s41594-019-0364-1

Abstract

Some proteins require completion of folding before translocation across a membrane into another cellular compartment. Yet the permeability barrier of the membrane should not be compromised and mechanisms have remained mostly elusive. Here, we present the structure of Saccharomyces cerevisiae Bcs1, an AAA-ATPase of the inner mitochondrial membrane. Bcs1 facilitates the translocation of the Rieske protein, Rip1, which requires folding and incorporation of a 2Fe-2S cluster before translocation and subsequent integration into the bc1 complex. Surprisingly, Bcs1 assembles into exclusively heptameric homo-oligomers, with each protomer consisting of an amphipathic transmembrane helix, a middle domain and an ATPase domain. Together they form two aqueous vestibules, the first being accessible from the mitochondrial matrix and the second positioned in the inner membrane, with both separated by the seal-forming middle domain. On the basis of this unique architecture, we propose an airlock-like translocation mechanism for folded Rip1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATPases Associated with Diverse Cellular Activities / chemistry
ATPases Associated with Diverse Cellular Activities / metabolism*
Electron Transport Complex III / chemistry
Electron Transport Complex III / metabolism
Mitochondrial Membranes / chemistry
Mitochondrial Membranes / metabolism
Mitochondrial Proteins / chemistry
Mitochondrial Proteins / metabolism*
Models, Molecular
Molecular Chaperones / chemistry
Molecular Chaperones / metabolism*
Nuclear Pore Complex Proteins / chemistry
Nuclear Pore Complex Proteins / metabolism*
Protein Conformation
Protein Domains
Protein Folding
Protein Multimerization
Protein Transport
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / metabolism*

Substances

BCS1 protein, S cerevisiae
Mitochondrial Proteins
Molecular Chaperones
NUP42 protein, S cerevisiae
Nuclear Pore Complex Proteins
Saccharomyces cerevisiae Proteins
ATPases Associated with Diverse Cellular Activities
Electron Transport Complex III