Protonation-dependent conformational variability of intrinsically disordered proteins
Leonhard Geist, Morkos A. Henen, Sandra Haiderer, Thomas C. Schwarz, Dennis Kurzbach, Anna Zawadzka-Kazimierczuk, Saurabh Saxena, Szymon Żerko, Wiktor Koźmiński, Dariush Hinderberger, Robert Konrat
Intrinsically disordered proteins (IDPs) are characterized by substantial conformational plasticity and undergo rearrangements of the time-averaged conformational ensemble upon changes of environmental conditions (e.g., in ionic strength, pH, molecular crowding). In contrast to stably folded proteins, IDPs often form compact conformations at acidic pH. The biological relevance of this process was, for example, demonstrated by NMR studies of the aggregation prone (low pH) state of α-Synuclein. Here we report a large-scale analysis of the pH dependence of disordered proteins using the recently developed meta-structure approach. The meta-structure analysis of a large set of intrinsically disordered proteins revealed a significant tendency of IDPs to form α-helical secondary structure elements and to preferentially fold into more compact structures under acidic conditions. The predictive validity of this novel approach was demonstrated with applications to the tumor-suppressor BASP1 and the transcription factor Tcf4.
