Exploring Flexibility and Folding Patterns Throughout Time in Voltage Sensors.

The voltage-sensing domain (VSD) is a module capable of responding to changes in the membrane potential through conformational changes and facilitating electromechanical coupling to open a pore gate, activate proton permeation pathways, or promote enzymatic activity in some membrane-anchored phosphatases. To carry out these functions, this module acts cooperatively through conformational changes. The VSD is formed by four transmembrane segments (S1-S4) but the S4 segment is critical since it carries positively charged residues, mainly Arg or Lys, which require an aqueous environment for its proper function.

Relation between flexibility and intrinsically disorder regions in thermosensitive TRP channels reveal allosteric effects.

How a protein propagates the conformational changes throughout its structure remains largely unknown. In thermosensitive TRP channels, this allosteric communication is triggered by ligand interaction or in response to temperature changes. Because dynamic allostery suggests a dynamic role of disordered regions, in this work we set out to thoroughly evaluate these regions in six thermosensitive TRP channels.

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

Structural evidence and much experimental data have demonstrated the presence of non-canonical helical substructures (π and 3) 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-3 transitions are mainly leagued with high local flexibility profiles.