7KPI

Crystal structure of the SPOP MATH domain

7KPI の概要

• エントリーDOI: 10.2210/pdb7kpi/pdb
• 分子名称: Speckle-type POZ protein (2 entities in total)
• 機能のキーワード: ubiquitin, ligase, adaptor, protein, gene regulation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16352.82

構造登録者

Usher, E.T.,Boal, A.K. (登録日: 2020-11-11, 公開日: 2021-04-28, 最終更新日: 2023-10-18)

主引用文献

Usher, E.T.,Sabri, N.,Rohac, R.,Boal, A.K.,Mittag, T.,Showalter, S.A.
Intrinsically disordered substrates dictate SPOP subnuclear localization and ubiquitination activity.
J.Biol.Chem., 296:100693-100693, 2021

PubMed Abstract: Speckle-type POZ protein (SPOP) is a ubiquitin ligase adaptor that binds substrate proteins and facilitates their proteasomal degradation. Most SPOP substrates present multiple SPOP-binding (SB) motifs and undergo liquid-liquid phase separation with SPOP. Pancreatic and duodenal homeobox 1 (Pdx1), an insulin transcription factor, is downregulated by interaction with SPOP. Unlike other substrates, only one SB motif has previously been reported within the Pdx1 C-terminal intrinsically disordered region (Pdx1-C). Given this difference, we aimed to determine the specific mode of interaction of Pdx1 with SPOP and how it is similar or different to that of other SPOP substrates. Here, we identify a second SB motif in Pdx1-C, but still find that the resulting moderate valency is insufficient to support phase separation with SPOP in cells. Although Pdx1 does not phase separate with SPOP, Pdx1 and SPOP interaction prompts SPOP relocalization from nuclear speckles to the diffuse nucleoplasm. Accordingly, we find that SPOP-mediated ubiquitination activity of Pdx1 occurs in the nucleoplasm and that highly efficient Pdx1 turnover requires both SB motifs. Our results suggest that the subnuclear localization of SPOP-substrate interactions and substrate ubiquitination may be directed by the properties of the substrate itself.

PubMed: 33894201
DOI: 10.1016/j.jbc.2021.100693

実験手法

X-RAY DIFFRACTION (1.7 Å)