Details

Autor(en) / Beteiligte

• Bauer, Valentin
• Schmidtgall, Boris
• Gógl, Gerg
• Dolenc, Jozica
• Osz, Judit
• Nominé, Yves
• Kostmann, Camille
• Cousido-Siah, Alexandra
• Mitschler, André
• Rochel, Natacha
• Travé, Gilles
• Kieffer, Bruno
• Torbeev, Vladimir

Titel

Conformational editing of intrinsically disordered protein by α-methylation

Ist Teil von

• Chemical science (Cambridge), 2021-01, Vol.12 (3), p.18-189

Ort / Verlag

Cambridge: Royal Society of Chemistry

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. Control of protein conformation was achieved for intrinsically disordered protein by incorporation of α-methylated amino acids.