Structural highlights
Function
SORCN_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 PubMed
Sorcin 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
- ↑ Matsumoto T, Hisamatsu Y, Ohkusa T, Inoue N, Sato T, Suzuki S, Ikeda Y, Matsuzaki M. Sorcin interacts with sarcoplasmic reticulum Ca(2+)-ATPase and modulates excitation-contraction coupling in the heart. Basic Res Cardiol. 2005 May;100(3):250-62. PMID:15754088 doi:10.1007/s00395-005-0518-7
- ↑ Colotti G, Zamparelli C, Verzili D, Mella M, Loughrey CM, Smith GL, Chiancone E. The W105G and W99G sorcin mutants demonstrate the role of the D helix in the Ca(2+)-dependent interaction with annexin VII and the cardiac ryanodine receptor. Biochemistry. 2006 Oct 17;45(41):12519-29. PMID:17029407 doi:10.1021/bi060416a
- ↑ Ilari A, Johnson KA, Nastopoulos V, Verzili D, Zamparelli C, Colotti G, Tsernoglou D, Chiancone E. The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein. J Mol Biol. 2002 Mar 29;317(3):447-58. PMID:11922676 doi:10.1006/jmbi.2002.5417
