Molecular architecture of the ankyrin SOCS box family of Cul5-dependent E3 ubiquitin ligases.

Muniz, JR; Guo, K; Kershaw, NJ; Ayinampudi, V; von Delft, F; Babon, JJ; Bullock, AN

Author(s): Muniz, JR; Guo, K; Kershaw, NJ; Ayinampudi, V; von Delft, F; Babon, JJ; Bullock, AN;
Details: Publication Year 2013-09-09,Volume 425,Issue #17,Page 3166-3177
Journal Title: Journal of Molecular Biology
Publication Type: Journal Article
Abstract: Multi-subunit Cullin-RING E3 ligases often use repeat domain proteins as substrate-specific adaptors. Structures of these macromolecular assemblies are determined for the F-box-containing leucine-rich repeat and WD40 repeat families, but not for the suppressor of cytokine signaling (SOCS)-box-containing ankyrin repeat proteins (ASB1-18), which assemble with Elongins B and C and Cul5. We determined the crystal structures of the ternary complex of ASB9-Elongin B/C as well as the interacting N-terminal domain of Cul5 and used structural comparisons to establish a model for the complete Cul5-based E3 ligase. The structures reveal a distinct architecture of the ASB9 complex that positions the ankyrin domain coaxial to the SOCS box-Elongin B/C complex and perpendicular to other repeat protein complexes. This alternative architecture appears favorable to present the ankyrin domain substrate-binding site to the E2-ubiquitin, while also providing spacing suitable for bulky ASB9 substrates, such as the creatine kinases. The presented Cul5 structure also differs from previous models and deviates from other Cullins via a rigid-body rotation between Cullin repeats. This work highlights the adaptability of repeat domain proteins as scaffolds in substrate recognition and lays the foundation for future structure-function studies of this important E3 family.
Publisher: Elsevier
Keywords: SOCS box protiens ; proteasome ; signaling ; ubiquitination; degradation ; protein–protein interaction
Research Division(s): Structural Biology; Cancer And Haematology
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779351/
Publisher's Version: https://doi.org/10.1016/j.jmb.2013.06.015
Terms of Use/Rights Notice: Copyright © 2013 The Authors. Published by Elsevier Ltd. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Creation Date: 2013-09-09 12:00:00