Molecular insights into degron recognition by CRL5ASB7 ubiquitin ligase

Mengyu Zhou, Xiaolu Wang, Jiangtao Li, Jinfeng Ma, Ziyu Bao, Xiaojie Yan, Bing Zhang, Tong Liu, Ying Yu (), Wenyi Mi () and Cheng Dong ()
Additional contact information
Mengyu Zhou: Tianjin Medical University
Xiaolu Wang: Tianjin Medical University
Jiangtao Li: Tianjin Medical University
Jinfeng Ma: Tianjin Medical University
Ziyu Bao: Tianjin Medical University
Xiaojie Yan: Tianjin Medical University
Bing Zhang: Tianjin Medical University
Tong Liu: Second Hospital of Tianjin Medical University
Ying Yu: Tianjin Medical University
Wenyi Mi: Tianjin Medical University
Cheng Dong: Tianjin Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50556-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50556-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50556-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().