Refinement of the structure of human Rab5a GTPase domain at 1.05 Å resolution

Rab5 is a GTPase that regulates early endosome fusion. Its GTPase domain crystal structure is reported here at 1.05 Å resolution in complex with a GTP-analog molecule. It provides the highest resolution three-dimensional model so far obtained for proteins from the Ras-like GTPase family. This study allows extension of structural examination of the GTPase machinery as well as of high-resolution protein structures in general. For example, a buried water-molecule network was observed underneath the switch regions, which is consistent with the functional roles of these regions in the molecular-switching process. Furthermore, residues of multiple conformation and clustered distribution of anisotropic thermal motions of the protein molecule may have general implications for the function of Ras-like GTPases.