7ZDD

Crystal structure of TRIM33 PHD-Bromodomain isoform B in complex with H3K10ac histone peptide.

7ZDD の概要

• エントリーDOI: 10.2210/pdb7zdd/pdb
• 関連するPDBエントリー: 5MR8
• 分子名称: E3 ubiquitin-protein ligase TRIM33, Histone H3.X, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: e3 ubiquitin-protein ligase, acetylation, transcription
• 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: 23828.29

構造登録者

Caria, S.,Duclos, S.,Crespillo, S.,Errey, J.,Barker, J.J. (登録日: 2022-03-29, 公開日: 2022-06-29, 最終更新日: 2024-11-13)

主引用文献

Sekirnik, A.R.,Reynolds, J.K.,See, L.,Bluck, J.P.,Scorah, A.R.,Tallant, C.,Lee, B.,Leszczynska, K.B.,Grimley, R.L.,Storer, R.I.,Malattia, M.,Crespillo, S.,Caria, S.,Duclos, S.,Hammond, E.M.,Knapp, S.,Morris, G.M.,Duarte, F.,Biggin, P.C.,Conway, S.J.
Identification of Histone Peptide Binding Specificity and Small-Molecule Ligands for the TRIM33 alpha and TRIM33 beta Bromodomains.
Acs Chem.Biol., 17:2753-2768, 2022

PubMed Abstract: TRIM33 is a member of the tripartite motif (TRIM) family of proteins, some of which possess E3 ligase activity and are involved in the ubiquitin-dependent degradation of proteins. Four of the TRIM family proteins, TRIM24 (TIF1α), TRIM28 (TIF1β), TRIM33 (TIF1γ) and TRIM66, contain C-terminal plant homeodomain (PHD) and bromodomain (BRD) modules, which bind to methylated lysine (KMe) and acetylated lysine (KAc), respectively. Here we investigate the differences between the two isoforms of TRIM33, TRIM33α and TRIM33β, using structural and biophysical approaches. We show that the N1039 residue, which is equivalent to N140 in BRD4(1) and which is conserved in most BRDs, has a different orientation in each isoform. In TRIM33β, this residue coordinates KAc, but this is not the case in TRIM33α. Despite these differences, both isoforms show similar affinities for H3K18Ac, and bind preferentially to H3K9MeK18Ac. We used this information to develop an AlphaScreen assay, with which we have identified four new ligands for the TRIM33 PHD-BRD cassette. These findings provide fundamental new information regarding which histone marks are recognized by both isoforms of TRIM33 and suggest starting points for the development of chemical probes to investigate the cellular function of TRIM33.

PubMed: 36098557
DOI: 10.1021/acschembio.2c00266

実験手法

X-RAY DIFFRACTION (1.625 Å)