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Structural and biochemical basis of Yos9 protein dimerization and possible contribution to self-association of 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation ubiquitin-ligase complex

Authors

  • J. Hanna
  • A. Schütz
  • F. Zimmermann
  • J. Behlke
  • T. Sommer
  • U. Heinemann

Journal

  • Journal of Biological Chemistry

Citation

  • J Biol Chem 287 (11): 8633-8640

Abstract

  • In yeast, the membrane-bound HRD ubiquitin ligase complex is a key player of the ER-associated protein degradation pathway that targets misfolded proteins for proteolysis. Yos9, a component of the luminal sub-module of the ligase, scans proteins for specific oligo-saccharide modifications, which constitute a critical determinant of the degradation signal. Here, we report the crystal structure of the Yos9 domain that was previously suggested to confer binding to Hrd3, another component of the HRD complex. We observe an αβ-roll domain architecture and a dimeric assembly which is confirmed by analytical ultracentrifugation of both the crystallized domain and full-length Yos9. Our binding studies indicate that, instead of this domain, the N-terminal part of Yos9 including the mannose-6-phosphate receptor homology domain mediates the association with Hrd3 in vitro. Our results support the model of a dimeric state of the HRD complex and provide first-time evidence of self-association on its luminal side.


DOI

doi:10.1074/jbc.M111.317644