3ZKJ

Crystal Structure of Ankyrin Repeat and Socs Box-Containing Protein 9 (Asb9) in Complex with Elonginb and Elonginc

Replaces:  2XAI

Summary for 3ZKJ

• Entry DOI: 10.2210/pdb3zkj/pdb
• Related: 2WZK
• Descriptor: ANKYRIN REPEAT AND SOCS BOX PROTEIN 9, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 1, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 2, ... (7 entities in total)
• Functional Keywords: transcription, transcription regulation, autoantibody
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Mitochondrion : Q96DX5; Nucleus : Q15369 Q15370
• Total number of polymer chains: 6
• Total formula weight: 105403.17

Authors

Muniz, J.R.C.,Guo, K.,Zhang, Y.,Ayinampudi, V.,Savitsky, P.,Keates, T.,Filippakopoulos, P.,Vollmar, M.,Yue, W.W.,Krojer, T.,Ugochukwu, E.,von Delft, F.,Knapp, S.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Bullock, A.N. (deposition date: 2013-01-23, release date: 2013-01-30, Last modification date: 2024-05-08)

Primary citation

Muniz, J.R.C.,Guo, K.,Kershaw, N.J.,Ayinampudi, V.,von Delft, F.,Babon, J.J.,Bullock, A.N.
Molecular Architecture of the Ankyrin Socs Box Family of Cul5-Dependent E3 Ubiquitin Ligases
J.Mol.Biol., 425:3166-, 2013

PubMed 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.

PubMed: 23806657
DOI: 10.1016/J.JMB.2013.06.015

Experimental method

X-RAY DIFFRACTION (2.58 Å)