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Význam nabitých reziduí pro aktivaci a modulaci iontového kanálu TRPA1 / The role of charged residues in the activation and modulation of the TRPA1 ion channelZímová, Lucie January 2015 (has links)
Important receptor for sensing painful stimuli is ion channel TRPA1, which is expressed in peripheral endings of nociceptive neurons, where it serves as transducer of physical and chemical environmental signals to the language of the nervous system. The effort to understand the mechanisms of its activity on a molecular level is driven by the vision of progress in treatment of chronic pain in humans. Our work focused on C-terminal cytoplasmic domain of TRPA1 receptor, where we described i.a. the probable binding site for calcium, which is the most important TRPA1 modulator. Using the combination of homology modeling and molecular dynamic simulations with electrophysiological measurements we were able to explain molecular basis of familial pain syndrome caused by TRPA1 point mutation. We contributed to the understanding of the TRPA1 voltage-dependent activation mechanism by describing the amino acids in proximal C-terminus and in S4-S5 linker of transmembrane domain that are directly involved in voltage-dependent gating. Powered by TCPDF (www.tcpdf.org)
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