Conformational editing of intrinsically disordered protein by α-methylation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Chemical Science Année : 2021

Conformational editing of intrinsically disordered protein by α-methylation

Jozica Dolenc
Judit Osz
  • Fonction : Auteur

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
Fichier principal
Vignette du fichier
islandora_140794.pdf (1.35 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03406169 , version 1 (09-05-2022)

Identifiants

Citer

Valentin Bauer, Boris Schmidtgall, Gergő Gógl, Jozica Dolenc, Judit Osz, et al.. Conformational editing of intrinsically disordered protein by α-methylation. Chemical Science, 2021, 12 (3), pp.1080-1089. ⟨10.1039/D0SC04482B⟩. ⟨hal-03406169⟩
33 Consultations
10 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More