8DWS

Full-length E47K SPOP

8DWS の概要

• エントリーDOI: 10.2210/pdb8dws/pdb
• EMDBエントリー: 27758
• 分子名称: Speckle-type POZ protein (1 entity in total)
• 機能のキーワード: spop, ubiquitination, cullin, oncoprotein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 295283.95

構造登録者

Cuneo, M.J.,Mittag, T.,O'Flynn, B.,Lo, Y.H. (登録日: 2022-08-02, 公開日: 2023-01-18, 最終更新日: 2024-11-20)

主引用文献

Cuneo, M.J.,O'Flynn, B.G.,Lo, Y.H.,Sabri, N.,Mittag, T.
Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation.
Mol.Cell, 83:731-745.e4, 2023

PubMed Abstract: The speckle-type POZ protein (SPOP) functions in the Cullin3-RING ubiquitin ligase (CRL3) as a receptor for the recognition of substrates involved in cell growth, survival, and signaling. SPOP mutations have been attributed to the development of many types of cancers, including prostate and endometrial cancers. Prostate cancer mutations localize in the substrate-binding site of the substrate recognition (MATH) domain and reduce or prevent binding. However, most endometrial cancer mutations are dispersed in seemingly inconspicuous solvent-exposed regions of SPOP, offering no clear basis for their cancer-causing and peculiar gain-of-function properties. Herein, we present the first structure of SPOP in its oligomeric form, uncovering several new interfaces important for SPOP self-assembly and normal function. Given that many previously unaccounted-for cancer mutations are localized in these newly identified interfaces, we uncover molecular mechanisms underlying dysregulation of SPOP function, with effects ranging from gross structural changes to enhanced self-association, and heightened stability and activity.

PubMed: 36693379
DOI: 10.1016/j.molcel.2022.12.033

実験手法

ELECTRON MICROSCOPY (3.73 Å)