Schulz, Jasmin, Avci, Donem, Queisser, Markus A., Gutschmidt, Aljona, Dreher, Lena-Sophie, Fenech, Emma J., Volkmar, Norbert ORCID: 0000-0003-0766-5606, Hayashi, Yuki, Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Christianson, John C. (2017). Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex formation for ER-associated degradation (ERAD). J. Cell Sci., 130 (19). S. 3322 - 3342. CAMBRIDGE: COMPANY OF BIOLOGISTS LTD. ISSN 1477-9137

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Abstract

The mammalian ubiquitin ligase Hrd1 is the central component of a complex facilitating degradation of misfolded proteins during the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD). Hrd1 associates with cofactors to execute ERAD, but their roles and how they assemble with Hrd1 are not well understood. Here, we identify crucial cofactor interaction domains within Hrd1 and report a previously unrecognised evolutionarily conserved segment within the intrinsically disordered cytoplasmic domain of Hrd1 (termed the HAF-H domain), which engages complementary segments in the cofactors FAM8A1 and Herp (also known as HERPUD1). This domain is required by Hrd1 to interact with both FAM8A1 and Herp, as well as to assemble higher-order Hrd1 complexes. FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schulz, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Avci, DonemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Queisser, Markus A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gutschmidt, AljonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreher, Lena-SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fenech, Emma J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volkmar, NorbertUNSPECIFIEDorcid.org/0000-0003-0766-5606UNSPECIFIED
Hayashi, YukiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoppe, ThorstenUNSPECIFIEDorcid.org/0000-0002-4734-9352UNSPECIFIED
Christianson, John C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-216736
DOI: 10.1242/jcs.206847
Journal or Publication Title: J. Cell Sci.
Volume: 130
Number: 19
Page Range: S. 3322 - 3342
Date: 2017
Publisher: COMPANY OF BIOLOGISTS LTD
Place of Publication: CAMBRIDGE
ISSN: 1477-9137
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RETICULUM-ASSOCIATED DEGRADATION; MAMMALIAN ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEIN; QUALITY-CONTROL; MISFOLDED PROTEINS; MUTANT ALPHA-1-ANTITRYPSIN; CONJUGATING ENZYME; HERP; DISLOCATION; STRESSMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21673

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