6V9H

Ankyrin repeat and SOCS-box protein 9 (ASB9), ElonginB (ELOB), and ElonginC (ELOC) bound to its substrate Brain-type Creatine Kinase (CKB)

Summary for 6V9H

• Entry DOI: 10.2210/pdb6v9h/pdb
• EMDB information: 21120 21121
• Descriptor: Creatine kinase B-type, Ankyrin repeat and SOCS box protein 9, Elongin-C, ... (4 entities in total)
• Functional Keywords: ankyrin repeat, elongation factor, creatine kinase, ubiquitin, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 143706.95

Authors

Komives, E.A.,Lumpkin, R.J.,Baker, R.W.,Leschziner, A.E. (deposition date: 2019-12-13, release date: 2020-04-29, Last modification date: 2024-10-30)

Primary citation

Lumpkin, R.J.,Baker, R.W.,Leschziner, A.E.,Komives, E.A.
Structure and dynamics of the ASB9 CUL-RING E3 Ligase.
Nat Commun, 11:2866-2866, 2020

PubMed Abstract: The Cullin 5 (CUL5) Ring E3 ligase uses adaptors Elongins B and C (ELOB/C) to bind different SOCS-box-containing substrate receptors, determining the substrate specificity of the ligase. The 18-member ankyrin and SOCS box (ASB) family is the largest substrate receptor family. Here we report cryo-EM data for the substrate, creatine kinase (CKB) bound to ASB9-ELOB/C, and for full-length CUL5 bound to the RING protein, RBX2, which binds various E2s. To date, no full structures are available either for a substrate-bound ASB nor for CUL5. Hydrogen-deuterium exchange (HDX-MS) mapped onto a full structural model of the ligase revealed long-range allostery extending from the substrate through CUL5. We propose a revised allosteric mechanism for how CUL-E3 ligases function. ASB9 and CUL5 behave as rigid rods, connected through a hinge provided by ELOB/C transmitting long-range allosteric crosstalk from the substrate through CUL5 to the RBX2 flexible linker.

PubMed: 32513959
DOI: 10.1038/s41467-020-16499-9

Experimental method

ELECTRON MICROSCOPY (4.1 Å)