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Structures of the platelet calcium‐ and integrin‐binding protein and the α IIb ‐integrin cytoplasmic domain suggest a mechanism for calcium‐regulated recognition; homology modelling and NMR studies
Author(s) -
Hwang P. M.,
Vogel H. J.
Publication year - 2000
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/(sici)1099-1352(200003/04)13:2<83::aid-jmr491>3.0.co;2-a
Subject(s) - calmodulin , cytoplasm , integrin , biophysics , calcium , biochemistry , peptide sequence , binding site , chemistry , protein structure , calcium in biology , biology , intracellular , cell , organic chemistry , gene
Calcium‐ and integrin‐binding protein (CIB) binds to the 20‐residue α IIb cytoplasmic domain of platelet α IIb β 3 integrin. Amino acid sequence similarities with calmodulin (CaM) and calcineurin B (CnB) allowed the construction of homology‐based models of calcium‐saturated CIB as well as apo‐CIB. In addition, the solution structure of the α IIb cytoplasmic domain in 45% aqueous trifluoroethanol was solved by conventional two‐dimensional NMR methods. The models indicate that the N‐terminal domain of CIB possesses a number of positively charged residues in its binding site that could interact with the acidic carboxy‐terminal LEEDDEEGE sequence of α IIb . The C‐terminal domain of CIB seems well‐suited to bind the sequence WKVGFFKR, which forms a well‐structured alpha helix; this is analogous to calmodulin and calcineurin B, which also bind alpha helices. Similarities between the C‐terminal domains of CIB and calmodulin suggest that binding of CIB to the cytoplasmic domain of α IIb may be affected by fluctuations in the intracellular calcium concentration. Copyright © 2000 John Wiley & Sons, Ltd.