PDBsum entry 3zkj

Transcription

PDB id: 3zkj

Contents

Protein chains

257 a.a.

82 a.a.

70 a.a.

105 a.a.

Ligands

EDO ×2

PEG

Metals

_CL ×2

Waters ×62

References listed in PDB file

Key reference

• Title: Molecular architecture of the ankyrin socs box family of cul5-Dependent e3 ubiquitin ligases.
• Authors: J.R.Muniz, K.Guo, N.J.Kershaw, V.Ayinampudi, F.Von delft, J.J.Babon, A.N.Bullock.
• Ref.: J Mol Biol, 2013, 425, 3166-3177. [DOI no: 10.1016/j.jmb.2013.06.015]
• PubMed id: 23806657

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.