Conformational editing of intrinsically disordered protein by α-methylation.
Journal
Chemical science
ISSN: 2041-6520
Titre abrégé: Chem Sci
Pays: England
ID NLM: 101545951
Informations de publication
Date de publication:
04 Nov 2020
04 Nov 2020
Historique:
entrez:
24
6
2021
pubmed:
25
6
2021
medline:
25
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34163874
doi: 10.1039/d0sc04482b
pii: d0sc04482b
pmc: PMC8178997
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1080-1089Informations de copyright
This journal is © The Royal Society of Chemistry.
Déclaration de conflit d'intérêts
There are no conflicts to declare.
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