6v9i
From Proteopedia
cryo-EM structure of Cullin5 bound to RING-box protein 2 (Cul5-Rbx2)
Structural highlights
Function[SPG1_STRSG] Binds to the constant Fc region of IgG with high affinity. [RBX2_MOUSE] Probable component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (By similarity). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (By similarity). Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme to the complex and brings it into close proximity to the substrate. Promotes the neddylation of CUL5 via its interaction with UBE2F. May play a role in protecting cells from apoptosis induced by redox agents (By similarity).[UniProtKB:P62877][UniProtKB:Q9UBF6] Publication Abstract from PubMedThe 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. Structure and dynamics of the ASB9 CUL-RING E3 Ligase.,Lumpkin RJ, Baker RW, Leschziner AE, Komives EA Nat Commun. 2020 Jun 8;11(1):2866. doi: 10.1038/s41467-020-16499-9. PMID:32513959[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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