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-Structure paper
Title | Structure and dynamics of the ASB9 CUL-RING E3 Ligase. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 2866, Year 2020 |
Publish date | Jun 8, 2020 |
Authors | Ryan J Lumpkin / Richard W Baker / Andres E Leschziner / Elizabeth A Komives / |
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- ...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. |
External links | Nat Commun / PubMed:32513959 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.1 - 5.2 Å |
Structure data | EMDB-21120, PDB-6v9h: EMDB-21121, PDB-6v9i: |
Chemicals | ChemComp-ZN: |
Source |
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Keywords | TRANSCRIPTION / Ankyrin repeat / Elongation Factor / Creatine Kinase / Ubiquitin / LIGASE / E3 Ubiquitin Ligase / RING-box protein |