9HFV

MyD88 peptide_2 bound to SPOP MATH domain

9HFV の概要

• エントリーDOI: 10.2210/pdb9hfv/pdb
• 分子名称: Speckle-type POZ protein, Myeloid differentiation primary response protein MyD88 (3 entities in total)
• 機能のキーワード: ubiquitination, ligase, immune signalling, degradation
• 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: 18321.08

構造登録者

Makhlouf, L.,Zeqiraj, E. (登録日: 2024-11-18, 公開日: 2025-06-18, 最終更新日: 2025-07-23)

主引用文献

Makhlouf, L.,Mishra, M.,Makhlouf, H.,Manfield, I.,Busino, L.,Zeqiraj, E.
Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.
Biochem.J., 482:583-600, 2025

PubMed Abstract: The adaptor protein, speckle-type BTB/POZ protein (SPOP), recruits substrates to the cullin-3-subclass of E3 ligase for selective protein ubiquitylation. The Myddosome protein, myeloid differentiation primary response 88 (MyD88), is ubiquitylated by the SPOP-based E3 ligase to negatively regulate immune signaling; however, the sequence rules for SPOP-mediated substrate engagement and degradation are not fully understood. Here, we show that MyD88 interacts with SPOP through a long degron that contains the established SPOP-binding consensus and an N-terminal site that we name the Q-motif. Based on the sequence similarity to MyD88, we show that additional substrates, including steroid receptor coactivator-3, SET domain-containing protein 2, and Caprin1, engage SPOP in this manner. We show that the Q-motif is a critical determinant of these interactions in mammalian cells and determine X-ray crystal structures that show the molecular basis of SPOP associations with these proteins. These studies reveal a new consensus sequence for substrate-binding to SPOP that is necessary for substrate ubiquitylation, thus expanding the sequence rules required for SPOP-mediated E3 ligase substrate recognition.

PubMed: 40178506
DOI: 10.1042/BCJ20253041

実験手法

X-RAY DIFFRACTION (1.45 Å)