6sqc
From Proteopedia
Crystal structure of complex between nuclear coactivator binding domain of CBP and [1040-1086]ACTR containing alpha-methylated Leu1055 and Leu1076
Structural highlights
DiseaseCBP_HUMAN Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:180849. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.[1] [2] [3] [4] FunctionMALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.CBP_HUMAN Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.[5] [6] [7] [8] Publication Abstract from PubMedIntrinsically 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 alpha-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 alpha-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 alpha-methylated amino acids are localized within alpha-helices in the bound state. This study demonstrates a strategy for characterization of individual conformational states of IDPs. Conformational editing of intrinsically disordered protein by alpha-methylation.,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 Chem Sci. 2020 Nov 4;12(3):1080-1089. doi: 10.1039/d0sc04482b. PMID:34163874[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Escherichia coli K-12 | Homo sapiens | Large Structures | Bauer V | Cousido-Siah A | Dolenc j | Gogl G | Kieffer B | Kostmann C | Mitschler A | Osz J | Rochel N | Schmidtgall B | Torbeev V | Trave G
