| Description |
Channels play crucial roles in signal transduction of various cell types. They come in various types and architecture, and are activated by variety of stimuli. In this presentation I will focus on solid-state NMR (ssNMR) studies on proteoliposmal preparation of a large ion channel (4x355 residues) that is activated upon binding cyclic nucleotides. The aim of the study is to comprehend the molecular events that relay ligand binding to channel activation that is not well understood. Using two – and three-dimensional ssNMR experiments under magic angle spinning, we identified lipids associated with the transmembrane domain that encompasses an S1-S4 voltage sensing domain and the canonical pore (S5-S6) architecture. According to our studies, ligand binding not only induces significant structural and dynamical rearrangements within the ligand-binding domain, but also affects the voltage-sensor domain and the pore region in complex with cAMP. Comparing these results to studies of the isolated ligand -binding-domain provides insight into the conformational degrees of freedom of the different channel domains that may be relevant during the transition of CNBD from the inactive to the ligand-bound active configuration. In addition to studies on ion channels, we are developing approaches to extend ssNMR-based lipid studies to cellular preparations of other channel types on two fronts, them being: 1. Bacteriophage fibers that serves as a conduit to transfer nucleic acids during bacterial infection. 2. Characterizing secretory system complex in bacterial cellular envelope, which is involved in pathogenesis |