Structures of the platelet calcium- And integrin-Binding protein and the alphaiib-Integrin cytoplasmic domain suggest a mechanism for calcium-Regulated recognition; homology modelling and nmr studies.
Calcium- and integrin-binding protein (CIB) binds to the 20-residue alphaIIb
cytoplasmic domain of platelet alphaIIbbeta3 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 alphaIIb 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 alphaIIb. 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
alphaIIb may be affected by fluctuations in the intracellular calcium
concentration.
