6SQC

Crystal structure of complex between nuclear coactivator binding domain of CBP and [1040-1086]ACTR containing alpha-methylated Leu1055 and Leu1076

6SQC の概要

• エントリーDOI: 10.2210/pdb6sqc/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Maltose/maltodextrin-binding periplasmic protein,CREB-binding protein, Nuclear receptor coactivator 3, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: complex, unnatural amino acid, protein binding
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51957.33

構造登録者

Bauer, V.,Schmidtgall, B.,Gogl, G.,Dolenc, j.,Osz, J.,Kostmann, C.,Mitschler, A.,Cousido-Siah, A.,Rochel, N.,Trave, G.,Kieffer, B.,Torbeev, V. (登録日: 2019-09-03, 公開日: 2020-09-30, 最終更新日: 2024-10-16)

主引用文献

Bauer, V.,Schmidtgall, B.,Gogl, G.,Dolenc, J.,Osz, J.,Nomine, Y.,Kostmann, C.,Cousido-Siah, A.,Mitschler, A.,Rochel, N.,Trave, G.,Kieffer, B.,Torbeev, V.
Conformational editing of intrinsically disordered protein by alpha-methylation.
Chem Sci, 12:1080-1089, 2020

PubMed Abstract: Intrinsically disordered proteins (IDPs) constitute a large portion of "Dark Proteome" - difficult to characterize or yet to be discovered protein structures. Here we used conformationally constrained α-methylated amino acids to bias the conformational ensemble in the free unstructured activation domain of transcriptional coactivator ACTR. Different sites and patterns of substitutions were enabled by chemical protein synthesis and led to distinct populations of α-helices. A specific substitution pattern resulted in a substantially higher binding affinity to nuclear coactivator binding domain (NCBD) of CREB-binding protein, a natural binding partner of ACTR. The first X-ray structure of the modified ACTR domain - NCBD complex visualized a unique conformation of ACTR and confirmed that the key α-methylated amino acids are localized within α-helices in the bound state. This study demonstrates a strategy for characterization of individual conformational states of IDPs.

PubMed: 34163874
DOI: 10.1039/d0sc04482b

実験手法

X-RAY DIFFRACTION (2.28 Å)