The crystal structure of rna1p: a new fold for a GTPase-activating protein.
rna1p is the Schizosaccharomyces pombe ortholog of the mammalian GTPase-activating protein (GAP) of Ran. Both proteins are essential for nuclear transport. Here, we report the crystal structure of rna1p at 2.66 A resolution. It contains 11 leucine-rich repeats that adopt the nonglobular shape of a crescent, bearing no resemblance to RhoGAP or RasGAP. The invariant residues of RanGAP form a contiguous surface, strongly indicating the Ran-binding interface. Alanine mutations identify Arg-74 as a critical residue for GTP hydrolysis. In contrast to RasGAP and RhoGAP, Arg-74 could be substituted by lysine and contributed significantly to the binding of Ran. Therefore, we suggest a GAP mechanism for rna1p, which constitutes a variation of the arginine finger mechanism found for Ras GAP and RhoGAP.
Max-Planck-Institut für molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany.
R C
RC
Hillig
L
L
Renault
I R
IR
Vetter
T
T
Drell
A
A
Wittinghofer
J
J
Becker
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007930:Leucine / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000737:chemistry* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D020931:ran GTP-Binding Protein; D020703:ras GTPase-Activating Proteins
D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; D011506:Proteins; D029702:Schizosaccharomyces pombe Proteins; D020703:ras GTPase-Activating Proteins; C085379:rho GTPase-activating protein; C499298:rna1 protein, S pombe; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein; D007930:Leucine