1f4q

From Proteopedia

Revision as of 13:45, 15 February 2008

CRYSTAL STRUCTURE OF APO GRANCALCIN

Overview

Grancalcin is a Ca(2+)-binding protein expressed at high level in, neutrophils. It belongs to the PEF family, proteins containing five, EF-hand motifs and which are known to associate with membranes in, Ca(2+)-dependent manner. Prototypic members of this family are, Ca(2+)-binding domains of calpain. Our recent finding that grancalcin, interacts with L-plastin, a protein known to have actin bundling activity, suggests that grancalcin may play a role in regulation of adherence and, migration of neutrophils. The structure of human grancalcin has been, determined at 1.9 A resolution in the absence of calcium (R-factor of, 0.212 and R-free of 0.249) and at 2. 5 A resolution in the presence of, calcium (R-factor of 0.226 and R-free of 0.281). The molecule is, predominantly alpha-helical: it contains eight alpha-helices and only two, short stretches of two-stranded beta-sheets between the loops of paired, EF-hands. Grancalcin forms dimers through the association of the unpaired, EF5 hands in a manner similar to that observed in calpain, confirming this, mode of association as a paradigm for the PEF family. Only one Ca(2+) was, found per dimer under crystallization conditions that included CaCl(2)., This cation binds to EF3 in one molecule, while this site in the second, molecule of the dimer is unoccupied. This unoccupied site shows higher, mobility. The structure determined in the presence of calcium, although, does not represent a fully Ca(2+)-loaded form, suggests that calcium, induces rather small conformational rearrangements. Comparison with, calpain suggests further that the relatively small magnitude of, conformational changes invoked by calcium alone may be a characteristic, feature of the PEF family. Moreover, the largest differences are localized, to the EF1, thus supporting the notion that calcium signaling occurs, through this portion of the molecule and that it may involve the, N-terminal Gly/Pro rich segment. Electrostatic potential distribution, shows significant differences between grancalcin and calpain domain VI, demonstrating their distinct character.

Disease

Known diseases associated with this structure: Cone dystrophy-3 OMIM:[600364], Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency OMIM:[606857]

About this Structure

1F4Q is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of human grancalcin, a member of the penta-EF-hand protein family., Jia J, Han Q, Borregaard N, Lollike K, Cygler M, J Mol Biol. 2000 Jul 28;300(5):1271-81. PMID:10903868

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