Crystal structure of the GAP domain of Gyp1p: first insights into interaction with Ypt/Rab proteins

We present the 1.9 Angstrom resolution crystal structure of the catalytic d omain of Gyp1p, a specific GTPase activating protein (GAP) for Ypt proteins , the yeast homologues of Rab proteins, which are involved in vesicular tra nsport. Gyp1p is a member of a large family of eukaryotic proteins with sha red sequence motifs, Previously, no structural information was available fo r any member of this class of proteins. The GAP domain of Gyp1p was found t o be fully alpha-helical. However, the observed fold does not superimpose w ith other alpha-helical GAPs (e.g. Ras- and Cdc42/Rho-GAP), The conserved a nd catalytically crucial arginine residue, identified by mutational analysi s, is in a comparable position to the arginine finger in the Ras- and Cdc42 -GAPs, suggesting that Gyp1p utilizes an arginine finger in the GAP reactio n, in analogy to Ras- and Cdc42-GAPs, A model for the interaction between G yp1p and the Ypt protein satisfying biochemical data is given.