Unknown

Dataset Information

0

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


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.

SUBMITTER: Muniz JR 

PROVIDER: S-EPMC3779351 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Muniz João R C JR   Guo Kunde K   Kershaw Nadia J NJ   Ayinampudi Vikram V   von Delft Frank F   Babon Jeffrey J JJ   Bullock Alex N AN  

Journal of molecular biology 20130625 17


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-term  ...[more]

Similar Datasets

| S-EPMC535916 | biostudies-literature
| S-EPMC7950132 | biostudies-literature
| S-EPMC4972691 | biostudies-literature
| S-EPMC3756526 | biostudies-literature
| S-EPMC5664961 | biostudies-literature
| S-EPMC9320238 | biostudies-literature
| S-EPMC1190250 | biostudies-literature
| S-EPMC2570371 | biostudies-literature
| S-EPMC4042170 | biostudies-literature
| S-EPMC6740566 | biostudies-literature