9TES

Crystal structure of beta-TrCP bound by diphosphorylated PDCD4 degron peptide

9TES の概要

• エントリーDOI: 10.2210/pdb9tes/pdb
• 分子名称: F-box/WD repeat-containing protein 1A, Programmed cell death protein 4, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: e3 ligase, phosphodegron, beta-trcp, i-kappa-b-alpha, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43402.34

構造登録者

Collie, W.G. (登録日: 2025-11-26, 公開日: 2026-04-08)

主引用文献

Collie, G.W.,Mak, H.,Acebron-Garcia-de-Eulate, M.,Argyrou, A.,Couturier, M.,Cuomo, M.E.,O Donovan, D.H.,Russell, I.C.,Wells, G.,Winter-Holt, J.
Structural Studies of beta TrCP Reveal Plasticity in Binding Modes of Consensus and Nonconsensus Degrons.
Acs Chem.Biol., 2026

PubMed Abstract: The E3 ligase βTrCP regulates a significant number of important cytosolic proteins by recognizing and binding to a "DSGXXS" consensus phosphodegron sequence, resulting in the ubiquitination and degradation of target proteins. While many of the substrates of βTrCP have strong disease links, there is high-resolution structural data available for just one of these proteins in complex with βTrCP. Here, we describe the development of a robust crystallographic system for βTrCP and report high-resolution crystal structures for βTrCP in complex with degrons from five new targets, encompassing the important cancer proteins, WEE1, claspin, ATF4, PDCD4, and IκBα. Interestingly, these structures reveal the molecular basis by which βTrCP can recognize and bind both consensus and nonconsensus degron peptides and reveal an overall general plasticity in degron binding mode. We also provide a biochemical assessment of the binding affinities of these peptides for βTrCP, adding further insight into the molecular interactions observed in the crystal structures. Finally, computational analyses of the βTrCP complexes identify opportunities for potential molecular glue approaches.

PubMed: 41891920
DOI: 10.1021/acschembio.5c01007

実験手法

X-RAY DIFFRACTION (1.217 Å)