PMC:4385177 / 9945-10920 JSONTXT

{"project":"2_test","denotations":[{"id":"25799108-14638856-2046587","span":{"begin":307,"end":309},"obj":"14638856"},{"id":"25799108-18634855-2046588","span":{"begin":311,"end":313},"obj":"18634855"},{"id":"25799108-1454850-2046589","span":{"begin":315,"end":317},"obj":"1454850"},{"id":"25799108-14638856-2046590","span":{"begin":542,"end":544},"obj":"14638856"}],"text":"In wild-type NCS proteins, binding of Ca2+ to their functional EF-hand domains operates a myristoyl switch mechanism—most extensively studied in the related neural protein recoverin—that controls the protein’s ability to translocate to target membranes and/or interact with downstream effectors (Figure S2).17, 18, 19 By means of this mechanism, NCS proteins, like hippocalcin, are able to act as reversible transducers of cellular Ca2+ signals and are thus capable of integrating both temporal and spatial aspects over a tight dynamic range.17 Thus, it is plausible to hypothesize that the homozygous p.Asn75Lys variant, by impairing or even preventing Ca2+ binding to EF-hand domain 2, would be expected to reduce the likelihood of conformational change of hippocalcin in response to Ca2+ signals and, by extension, result in a defect in cellular Ca2+ signal transduction in the striatum, an area of the brain intimately connected with movement disorders, such as dystonia."}