Stephane Jedele, "Study of the KCNN4 channel involved in the pathological dehydration of red blood cells using molecular modeling approaches"

Wednesday 9 Apr 2025, 12:15 → 13:15 Europe/Ljubljana

C/2-X - F1 čajnica (Jamova)

KCNN4 is a calcium (Ca)-activated potassium (K+) channel translocating K+ ions across several cellular membranes and for which Ca2+ sensitivity is conferred by calmodulin (CaM). Until the main part of the protein structure bound to CaM has been resolved, in silico studies had used homology models derived from the well characterized transmembrane domain of other K+ channels, limiting the functional investigation to this particular region. Thus, how the regulatory domains of KCNN4 communicate with each other and where the possible gates are located across the complete structure are still not well understood. My PhD work presents for the first time results obtained from an extensive investigation of full-length models of the channel in different conformational states and molecular contexts using all-atom molecular dynamics simulations and enhanced sampling methods. The results allow us to contextualize no less than 6 of the pathogenic mutations identified in the channel to date, and provide a new basis for understanding the KCNN4 function.