Calcium and integrin binding protein 1 (CIB1) is a specific binding partner for the cytoplasmic domain of the alpha IIb subunit of the highly abundant platelet integrin alpha IIb beta 3. This protein has been suggested to be involved in the regulation of the activation of alpha IIb beta 3, a process leading to platelet aggregation and blood coagulation. In this work, the solution structure of the deuterated Ca2+-CIB1 protein complexed with an alpha IIb peptide was first determined through modern RDC-based NMR methods. Next, we generated a complex structure for CIB1 and the alpha IIb domain (Ca2+-CIB1/alpha IIb) using the program Haddock, which is based on experimental restraints obtained for the protein peptide interface from cross-saturation NMR experiments. In this data-driven complex structure, the N-terminal alpha-helix of the cytoplasmic domain of alpha IIb is buried in the hydrophobic pocket of the C-lobe of Ca2+-CIB1. The C-terminal acidic tail of alpha IIb remains unstructured and likely interacts with several positively charged residues in the N-lobe of Ca2+-CIB1. A potential molecular mechanism for the CIB1-mediated activation of the platelet integrin could be proposed on the basis of the model structure of this protein complex. Another feature of this work is that, in the NMR cross-saturation experiments, we applied the selective radio frequency irradiation to the smaller binding partner (the alpha IIb peptide), and successfully detected the binding interface on the larger binding partner Ca2+-CIB1 through its selectively protonated methyl groups. This 'reverse' methodology has a broad potential to be employed to many other complexes where synthetic peptides and a suitably isotope-labeled medium-to large-sized protein are used to study protein protein interactions.