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IP\n                    <jats:sub>3<\/jats:sub>\n                    activates channels at a distance by reversible allosteric changes in the IP\n                    <jats:sub>3<\/jats:sub>\n                    R tetramer. Here we show a new mode of posttranslational modification that irreversibly blocks allosteric changes in the IP\n                    <jats:sub>3<\/jats:sub>\n                    R. We identified an IP\n                    <jats:sub>3<\/jats:sub>\n                    R-modifying enzyme as tissue transglutaminase that inhibits IP\n                    <jats:sub>3<\/jats:sub>\n                    R function by locking subunit configurations. This modification chronically impaired calcium signaling and autophagy regulation in living cells, and up-regulated modification was observed in Huntington disease models. To our knowledge, this is the first demonstration of transglutaminase-catalyzed posttranslational modification in ligand-gated channel allostery and provides a new framework for enzymatic regulation of allostery.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1409730111","type":"journal-article","created":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T00:38:33Z","timestamp":1410223113000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors"],"prefix":"10.1073","volume":"111","author":[{"given":"Kozo","family":"Hamada","sequence":"first","affiliation":[{"name":"Laboratory for Developmental Neurobiology, Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;"},{"name":"Calcium Oscillation Project, International 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