title: Crystal structure of the GAP domain of Gyp1p: first insights into interaction with Ypt/Rab proteins.
abstract: We present the 1.9 A resolution crystal structure of the catalytic domain of Gyp1p, a specific GTPase activating protein (GAP) for Ypt proteins, the yeast homologues of Rab proteins, which are involved in vesicular transport. Gyp1p is a member of a large family of eukaryotic proteins with shared sequence motifs. Previously, no structural information was available for any member of this class of proteins. The GAP domain of Gyp1p was found to be fully alpha-helical. However, the observed fold does not superimpose with other alpha-helical GAPs (e.g. Ras- and Cdc42/Rho-GAP). The conserved and catalytically crucial arginine residue, identified by mutational analysis, 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 reaction, in analogy to Ras- and Cdc42-GAPs. A model for the interaction between Gyp1p and the Ypt protein satisfying biochemical data is given.
authors.affiliation: Max-Planck-Institute for Molecular Physiology, Department of Physical Biochemistry, Otto-Hahn-Strasse 11, D-44227 Dortmund, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rak
authors.forename: R
authors.initials: R
authors.lastname: Fedorov
authors.forename: K
authors.initials: K
authors.lastname: Alexandrov
authors.forename: S
authors.initials: S
authors.lastname: Albert
authors.forename: R S
authors.initials: RS
authors.lastname: Goody
authors.forename: D
authors.initials: D
authors.lastname: Gallwitz
authors.forename: A J
authors.initials: AJ
authors.lastname: Scheidig
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D020690:GTPase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000737:chemistry; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000737:chemistry
chemical_list: D020690:GTPase-Activating Proteins; C416529:GYP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020703:ras GTPase-Activating Proteins; D006165:Guanylyl Imidodiphosphate; D001120:Arginine; C086866:VPS21 protein, S cerevisiae; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020691:rab GTP-Binding Proteins