The mechanism of protein: protein association will be investigated using the interaction of calmodulin (CaM) and several of its target proteins as a model system. Three dimensional solution structures of CaM bound to various proteins will be determined: 1) the interaction between CaM and peptides corresponding to the two consecutive binding sites in myr4 (myosin I from rat); and 2) the interaction between apoCaM and the whole neuronal protein, neurogranin. The first project will include a thermodynamic investigation of myr4 recognition by CaM, to understand the unusual Ca2+-dependence of the interaction. The CaM:neurogranin structure would represent the first complex of CaM bound to an entire protein. Additional pressure dependence studies will be used to further elucidate the mechanism of this Ca2+-independent interaction, and will require the use of a novel high pressure NMR techniques developed by the Wand group. If time allows, additional thermodynamic studies are proposed addressing the determinants of target recognition using chimeric peptide substrates.
| Kranz, James K; Lee, Eun K; Nairn, Angus C et al. (2002) A direct test of the reductionist approach to structural studies of calmodulin activity: relevance of peptide models of target proteins. J Biol Chem 277:16351-4 |
| Jaren, Olav R; Kranz, James K; Sorensen, Brenda R et al. (2002) Calcium-induced conformational switching of Paramecium calmodulin provides evidence for domain coupling. Biochemistry 41:14158-66 |
