Poster #RP208
Molecular Modeling of Calmodulin Bound to the IQ-Motifs of Myosin Va
Nelson Menetti*, Roy Larson*
*Universidade de São Paulo -FMRP , Ribeirão Preto , Brazil
Myosin-Va is a molecular motor with an elongated neck domain composed of six tandem IQ-motifs that bind calmodulins. Calcium regulates the mechanochemical activities of myosin Va via binding to the calmodulins bound to the neck domain. The structural determination of the IQ-calmodulin complexes of myosin V, however, has proved illusive. As a way to formulate hypotheses, we have generated a 3-D molecular model from sequence data of the complete neck domain of myosin Va using the freeware program ArgusLab. Its overall structure is a long, uninterrupted, basic, amphipathic alpha - helix with a slight curvature from amino - to carboxy - terminal. Docking of the crystal structure of calmodulin onto this model, using the freeware program Hex, has produced a plausible structure for the calmodulin-IQ1 complex. This has been refined by energy minimization and tested by correlation of the specific orientation of alpha - helices in the model with homologous alpha - helices in the known crystal structures of calmodulin-related proteins bound to IQ sequences. Docking of calmodulin to IQs 2 6 have shown more diversity in structural orientation and may reflect the diversity in binding properties of calmodulin to the different IQ sites.
Financial support from FAPESP, CNPq