Jan 21, 2017

Mechanistic basis for a molecular triage reaction

Science
Sichen ShaoRamanujan S Hegde

Abstract

Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. We reconstituted the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis. Commitment to ubiquitination is dictated primarily by comparatively slower client dissociation from SGTA and nonprivate capture by the BAG6 subunit of the quality control module. Our results provide a paradigm for how priority and time are encoded within a multichaperone triage system.

  • References45
  • Citations20

Citations

Mentioned in this Paper

SGTA protein, human
ASNA1 gene
Decision Making
Cellular Homeostasis
Protein Digestion
Membrane
BAG6 protein, human
ASNA1 protein, human
Protein Biosynthesis
Molecular Chaperones

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