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Crystal structure of ASB7-Elongin B/C bound to the LZTS1-degronCrystal structure of ASB7-Elongin B/C bound to the LZTS1-degron
Structural highlights
FunctionASB7_HUMAN Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.[1] Publication Abstract from PubMedThe ankyrin (ANK) SOCS box (ASB) family, encompassing ASB1-18, is the largest group of substrate receptors of cullin 5 Ring E3 ubiquitin ligase. Nonetheless, the mechanism of substrate recognition by ASB family proteins has remained largely elusive. Here we present the crystal structure of ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron. ASB7 employs its ANK3-6 to form an extended groove, effectively interacting with the internal alpha-helix-degron through a network of side-chain-mediated electrostatic and hydrophobic interactions. Our structural findings, combined with biochemical and cellular analyses, identify the key residues of the degron motif and ASB7 required for their recognition. This will facilitate the identification of additional physiological substrates of ASB7 by providing a defined degron motif for screening. Furthermore, the structural insights provide a basis for the rational design of compounds that can specifically target ASB7 by disrupting its interaction with its cognate degron. Molecular insights into degron recognition by CRL5(ASB7) ubiquitin ligase.,Zhou M, Wang X, Li J, Ma J, Bao Z, Yan X, Zhang B, Liu T, Yu Y, Mi W, Dong C Nat Commun. 2024 Jul 22;15(1):6177. doi: 10.1038/s41467-024-50556-x. PMID:39039081[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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