Non-canonical helical transitions and conformational switching are associated with characteristic flexibility and disorder indices in TRP and Kv channels

Channels (Austin). 2023 Dec;17(1):2212349. doi: 10.1080/19336950.2023.2212349.ABSTRACTStructural evidence and much experimental data have demonstrated the presence of non-canonical helical substructures (π and 310) in regions of great functional relevance both in TRP as in Kv channels. Through an exhaustive compositional analysis of the sequences underlying these substructures, we find that each of them is associated with characteristic local flexibility profiles, which in turn are implicated in significant conformational rearrangements and interactions with specific ligands. We found that α-to-π helical transitions are associated with patterns of local rigidity whereas α-to-310 transitions are mainly leagued with high local flexibility profiles. We also study the relationship between flexibility and protein disorder in the transmembrane domain of these proteins. By contrasting these two parameters, we located regions showing a sort of structural discrepancy between these similar but not identical protein attributes. Notably, these regions are presumably implicated in important conformational rearrangements during the gating in those channels. In that sense, finding these regions where flexibility and disorder are not proportional allows us to detect regions with potential functional dynamism. From this point of view, we highlighted some conformational rearrangements that occur during ligand binding events, the compaction, and refolding of the outer pore loops in several ...

Source: Channels - May 17, 2023 Category: Molecular Biology Authors: Abigail Garc ía-Morales Daniel Balleza Source Type: research