The crystal structure of rna1p: A new fold for a GTPase-activating protein

ma1p is the Schizosaccharomyces pombe ortholog of the mammalian GTPase-acti vating protein (GAP) of Ran. Both proteins are essential for nuclear transp ort. Here, we report the crystal structure of ma1p at 2.66 Angstrom resolut ion. It contains 11 leucine-rich repeats that adopt that nonglobular shape of a crescent, bearing no resemblance to RhoGAP or RasGAP. The invariant re sidues of RanGAP form a contiguous surface, strongly indicating the Ran-bin ding interface. Alanine mutations identify Arg-74 as a critical residue for GTP hydrolysis. In contrast to RasGAP and RhoGAP, Arg-74 could be substitu ted by lysine and contributed significantly to the binding of Ran. Therefor e, we suggest a GAP mechanism for ma1p, which constitutes a variation of th e arginine finger mechanism found for RasGAP and RhoGAP.