3o77
From Proteopedia
The structure of Ca2+ Sensor (Case-16)
Structural highlights
DiseaseCALM1_HUMAN The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. FunctionCALM1_HUMAN Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [4] MYLK_CHICK Phosphorylates a specific serine in the N-terminus of a myosin light chain, which leads to the formation of calmodulin/MLCK signal transduction complexes which allow selective transduction of calcium signals.GFP_AEQVI Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin. Publication Abstract from PubMedHere we report the first crystal structure of a high-contrast genetically encoded circularly permuted green fluorescent protein (cpGFP)-based Ca(2+) sensor, Case16, in the presence of a low Ca(2+) concentration. The structure reveals the positioning of the chromophore within Case16 at the first stage of the Ca(2+)-dependent response when only two out of four Ca(2+)-binding pockets of calmodulin (CaM) are occupied with Ca(2+) ions. In such a "half Ca(2+)-bound state", Case16 is characterized by an incomplete interaction between its CaM-/M13-domains. We also report the crystal structure of the related Ca(2+) sensor Case12 at saturating Ca(2+) concentration. Based on this structure, we postulate that cpGFP-based Ca(2+) sensors can form non-functional homodimers where the CaM-domain of one sensor molecule binds symmetrically to the M13-peptide of the partner sensor molecule. Case12 and Case16 behavior upon addition of high concentrations of free CaM or M13-peptide reveals that the latter effectively blocks the fluorescent response of the sensor. We speculate that the demonstrated intermolecular interaction with endogenous substrates and homodimerization can impede proper functioning of this type of Ca(2+) sensors in living cells. The structure of Ca2+ sensor Case16 reveals the mechanism of reaction to low Ca2+ concentrations.,Leder L, Stark W, Freuler F, Marsh M, Meyerhofer M, Stettler T, Mayr LM, Britanova OV, Strukova LA, Chudakov DM, Souslova EA Sensors (Basel). 2010;10(9):8143-60. Epub 2010 Aug 30. PMID:22163646[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Aequorea victoria | Gallus gallus | Homo sapiens | Large Structures | Britanova OV | Chudakov DM | Freuler F | Leder L | Marsh M | Mayr LM | Meyerhofer M | Stark W | Stettler T | Strukova LA
