Structural basis for tail-anchored membrane protein biogenesis by the Get3-receptor complex

Science. 2011 Aug 5;333(6043):758-62. doi: 10.1126/science.1207125. Epub 2011 Jun 30.

Abstract

Tail-anchored (TA) proteins are involved in cellular processes including trafficking, degradation, and apoptosis. They contain a C-terminal membrane anchor and are posttranslationally delivered to the endoplasmic reticulum (ER) membrane by the Get3 adenosine triphosphatase interacting with the hetero-oligomeric Get1/2 receptor. We have determined crystal structures of Get3 in complex with the cytosolic domains of Get1 and Get2 in different functional states at 3.0, 3.2, and 4.6 angstrom resolution. The structural data, together with biochemical experiments, show that Get1 and Get2 use adjacent, partially overlapping binding sites and that both can bind simultaneously to Get3. Docking to the Get1/2 complex allows for conformational changes in Get3 that are required for TA protein insertion. These data suggest a molecular mechanism for nucleotide-regulated delivery of TA proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / chemistry*
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cytosol / chemistry
  • Endoplasmic Reticulum / metabolism
  • Guanine Nucleotide Exchange Factors / chemistry*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Microsomes / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Adaptor Proteins, Vesicular Transport
  • GET1 protein, S cerevisiae
  • Get2 protein, S cerevisiae
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • Get3 protein, S cerevisiae

Associated data

  • PDB/3SJA
  • PDB/3SJB
  • PDB/3SJC
  • PDB/3SJD