| Popis: |
Gap junction channels are key pathways for direct cell-cell communication that enables the intercellular diffusion of ions, second messengers, small metabolites and electrical coupling. To date, there are over 20 members of the gap junction channel family identified in human and they serve distinct roles in different cells and tissues. Among them, Cx26 is one of the most prominently expressed connexins (including Cx26, 29, 30 and 43) in the cochlea, which is primarily responsible of sound transduction in the inner ear. Over 100 mutations of Cx26 genes account for the 14% of the hearing loss. Here, we report a novel calcium binding pocket conserved in various family of Cxs using our established computer algorithms. In addition, we have also identified a calmodulin regulation site that with many disease mutations reside proximately. using a variety of spectroscopic methods including CD, fluorescence, NMR, we have determined metal binding affinity, stoichiometry, conformational change and binding modes of Ca2+ and Calmodulin. |
