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Structure. 2016 Aug 2;24(8):1248-1256. doi: 10.1016/j.str.2016.05.016. Epub 2016 Jul 7.

Model of the Ankyrin and SOCS Box Protein, ASB9, E3 Ligase Reveals a Mechanism for Dynamic Ubiquitin Transfer.

Author information

1
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0378, USA.
2
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0378, USA; National Biomedical Computation Resource, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608, USA.
3
Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Santiago 7800003, Chile.
4
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0378, USA; National Biomedical Computation Resource, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608, USA. Electronic address: ramaro@ucsd.edu.
5
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0378, USA. Electronic address: ekomives@ucsd.edu.

Abstract

Cullin-RING E3 ligases (CRLs) are elongated and bowed protein complexes that transfer ubiquitin over 60 Å to proteins targeted for proteasome degradation. One such CRL contains the ankyrin repeat and SOCS box protein 9 (ASB9), which binds to and partially inhibits creatine kinase (CK). While current models for the ASB9-CK complex contain some known interface residues, the overall structure and precise interface of the ASB9-CK complex remains unknown. Through an integrative modeling approach, we report a third-generation model that reveals precisely the interface interactions and also fits the shape of the ASB9-CK complex as determined by small-angle X-ray scattering. We constructed an atomic model for the entire CK-targeting CRL to uncover dominant modes of motion that could permit ubiquitin transfer. Remarkably, only the correctly docked CK-containing E3 ligase and not incorrectly docked structures permitted close approach of ubiquitin to the CK substrate.

PMID:
27396830
PMCID:
PMC4972691
DOI:
10.1016/j.str.2016.05.016
[Indexed for MEDLINE]
Free PMC Article

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