Skip to Main content Skip to Navigation
New interface
Journal articles

Conformational editing of intrinsically disordered protein by α-methylation

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
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03406169
Contributor : Gilles TRAVE Connect in order to contact the contributor
Submitted on : Monday, May 9, 2022 - 11:02:17 PM
Last modification on : Thursday, May 12, 2022 - 11:50:08 AM

File

islandora_140794.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

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⟩

Share

Metrics

Record views

21

Files downloads

4