Structure of the extremely slow GTPase Rab6A in the GTP bound form at 1.8A resolution.
Rab/Ypt GTPases represent a>60 member large family of membrane traffic regulators in eukaryotic cells. Members of this group display intrinsic GTPase activity varying over two orders of magnitude. Here, we show that Rab6A represents the RabGTPase with the slowest spontaneous GTPase activity yet measured (5x10(-6)s(-1)). Due to the very low intrinsic hydrolysis rate we were able to crystallise and solve the structure of the Rab6A:GTP complex to 1.82A resolution. Analysis of the structure suggests that low catalytic activity of the Rab6A might be due to high flexibility of the Switch II region and a low degree of constraint of critically important for catalysis Gln 72.
Bergbrede
Tim
T
Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.
Pylypenko
Olena
O
Rak
Alexey
A
Alexandrov
Kirill
K
D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D017354:Point Mutation / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C094135:Rab6 protein; D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020691:rab GTP-Binding Proteins