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The X-ray structure of the Sorcin Calcium Binding Domain (SCBD) provides insight into the phosphorylation and calcium dependent processess
Structural highlights
FunctionSORCN_CRIGR Calcium-binding protein that modulates excitation-contraction coupling in the heart. Contributes to calcium homeostasis in the sarcoplasmic reticulum in the heart. Modulates the activity of RYR2 calcium channels.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSorcin is a 21.6 kDa calcium binding protein, expressed in a number of mammalian tissues that belongs to the small, recently identified penta-EF-hand (PEF) family. Like all members of this family, sorcin undergoes a Ca2+-dependent translocation from cytosol to membranes where it binds to target proteins. For sorcin, the targets differ in different tissues, indicating that it takes part in a number of Ca2+-regulated processes. The sorcin monomer is organized in two domains like in all PEF proteins: a flexible, hydrophobic, glycine-rich N-terminal region and a calcium binding C-terminal domain. In vitro, the PEF proteins are dimeric in their Ca2+-free form, but have a marked tendency to precipitate when bound to calcium. Stabilization of the dimeric structure is achieved by pairing of the uneven EF-hand, EF5. Sorcin can also form tetramers at acid pH.The sorcin calcium binding domain (SCBD, residues 33-198) expressed in Escherichia coli was crystallized in the Ca2+-free form. The structure was solved by molecular replacement and was refined to 2.2 A with a crystallographic R-factor of 22.4 %. Interestingly, the asymmetric unit contains two dimers.The structure of the SCBD leads to a model that explains the solution properties and describes the Ca2+-induced conformational changes. Phosphorylation studies show that the N-terminal domain hinders phosphorylation of SCBD, i.e. the rate of phosphorylation increased twofold in the absence of the N-terminal region. In addition, previous fluorescence studies indicated that hydrophobic residues are exposed to solvent upon Ca2+ binding to full-length sorcin. The model accounts for these data by proposing that Ca2+ binding weakens the interactions between the two domains and leads to their reorientation, which exposes hydrophobic regions facilitating the Ca2+-dependent binding to target proteins at or near membranes. The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein.,Ilari A, Johnson KA, Nastopoulos V, Verzili D, Zamparelli C, Colotti G, Tsernoglou D, Chiancone E J Mol Biol. 2002 Mar 29;317(3):447-58. PMID:11922676[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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