Seminar

Seminar on Molecular basis of thermoreceptors

Antonio Vicente Ferrer Montiel, PhD

Doctor Ferrer Montiel’s group focuses on understanding, in terms of structure-function, the coupling between the binding of an agonist and functional activation in thermoreceptors (TRPV1-V3 TRPM8 and TRPA1), a family of ion channels involved in signal transduction of thermal stimuli. To achieve this milestone, they use a combination of complementary approaches ranging from functional directed evolution to molecular modeling and resolution of atomic structure. Directed evolution is based on the endowment with thermal sensitivity to membranes proteins that lack it through the introduction of putative thermal sensors identified in thermoreceptors. The resulting chimeric proteins are functional assayed and domains are joined by direct and/or random mutagenesis. These studies allow us to identify the molecular determinants of thermal sensitivity and understanding how they are alosterically attached to the pore domain. As a result of these studies it is expected to design molecules that interfere with this functional coupling allowing correct pathological dysfunction of these channels. For this aim, the group has begun to obtain structural information of high resolution which unveils the molecular architecture of these channels. A priority goal is thus to solve the atomic structure of both mutants generated domains acting as temperature sensors and complete thermoreceptors. As a whole, this will have a dynamic picture of the process of "gating" channels and will contribute to the validation of new pharmacological targets.