REFINED SOLUTION STRUCTURE OF HUMAN PROFILIN-I

Profilin is a ubiquitous eukaryotic protein that binds to both cytosol ic actin and the phospholipid phosphatidylinositol-4,5-bisphosphate. T hese dual competitive binding capabilities of profilin suggest that pr ofilin serves as a link between the phosphatidyl inositol cycle and ac tin polymerization, and thus profilin may be an essential component in the signaling pathway leading to cytoskeletal rearrangement. The refi ned three-dimensional solution structure of human profilin I has been determined using multidimensional heteronuclear NMR spectroscopy. Twen ty structures were selected to represent the solution conformational e nsemble. This ensemble of structures has root-mean-square distance dev iations from the mean structure of 0.58 Angstrom for the backbone atom s and 0.98 Angstrom for all non-hydrogen atoms. Comparison of the solu tion structure of human profilin to the crystal structure of bovine pr ofilin reveals that, although profilin adopts essentially identical co nformations in both states, the solution structure is more compact tha n the crystal structure. Interestingly, the regions that show the most structural diversity are located at or near the actin-binding site of profilin. We suggest that structural differences are reflective of dy namical properties of profilin that facilitate favorable interactions with actin. The global folding pattern of human profilin also closely resembles that of Acanthamoeba profilin I, reflective of the 22% seque nce identity and similar to 45% sequence similarity between these two proteins.