Crystal structures of Ral-GppNHp and Ral-GDP reveal two binding sites that are also present in Ras and Rap.
RalA is a GTPase with effectors such as Sec5 and Exo84 in the exocyst complex and RalBP1, a GAP for Rho proteins. We report the crystal structures of Ral-GppNHp and Ral-GDP. Disordered switch I and switch II, located away from crystal contacts, are observed in one of the molecules in the asymmetric unit of the Ral-GppNHp structure. In the other molecule in the asymmetric unit, a second Mg(2+) ion is bound to the GppNHp gamma-phosphate in an environment in which switch I is pulled away from the nucleotide and switch II is found in a tight beta turn. Clustering of conserved residues on the surface of Ral-GppNHp identifies two putative sites for protein-protein interaction. One site is adjacent to switch I. The other is modulated by switch II and is obstructed in Ral-GDP. The Ral structures are discussed in the context of the published structures of the Ral/Sec5 complex, Ras, and Rap.
Nicely
Nathan I
NI
Department of Molecular and Structural Biochemistry, 128 Polk Hall-CB 7622, North Carolina State University, Raleigh, NC 27695, USA.
Kosak
Justin
J
de Serrano
Vesna
V
Mattos
Carla
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006153:Guanosine Diphosphate / Q000737:chemistry* / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D020668:rap GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism
D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020668:rap GTP-Binding Proteins; D018631:ras Proteins