8Y1U

Crystal structure of ASB7-Elongin B/C bound to the LZTS1-degron

Summary for 8Y1U

• Entry DOI: 10.2210/pdb8y1u/pdb
• Descriptor: Ankyrin repeat and SOCS box protein 7, Peptide from Leucine zipper putative tumor suppressor 1, Elongin-B, ... (5 entities in total)
• Functional Keywords: ubiquitin ligase, cytosolic protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 60327.94

Authors

Dong, C.,Yan, X.,Zhou, M. (deposition date: 2024-01-25, release date: 2024-12-04)

Primary citation

Zhou, M.,Wang, X.,Li, J.,Ma, J.,Bao, Z.,Yan, X.,Zhang, B.,Liu, T.,Yu, Y.,Mi, W.,Dong, C.
Molecular insights into degron recognition by CRL5 ASB7 ubiquitin ligase.
Nat Commun, 15:6177-6177, 2024

PubMed Abstract: The 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 α-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.

PubMed: 39039081
DOI: 10.1038/s41467-024-50556-x

Experimental method

X-RAY DIFFRACTION (2.41 Å)