6SQC

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

Summary for 6SQC

• Entry DOI: 10.2210/pdb6sqc/pdb
• Related PRD ID: PRD_900001
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,CREB-binding protein, Nuclear receptor coactivator 3, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: complex, unnatural amino acid, protein binding
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 2
• Total formula weight: 51957.33

Authors

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. (deposition date: 2019-09-03, release date: 2020-09-30, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.28 Å)