Comparative functional analysis of the Rac GTPases.
Small GTPases of the Rho family including Rac, Rho and Cdc42 regulate different cellular processes like reorganization of the actin cytoskeleton by acting as molecular switches. The three distinct mammalian Rac proteins share very high sequence identity but how their specificity is achieved is hitherto unknown. Here we show that Rac1 and Rac3 are very closely related concerning their biochemical properties, such as effector interaction, nucleotide binding and hydrolysis. In contrast, Rac2 displays a slower nucleotide association and is more efficiently activated by the Rac-GEF Tiam1. Modeling and normal mode analysis support the idea that altered dynamics of Rac2 at the switch I region may be responsible for different biochemical properties. These results provide insight into the individual functionalities of the Rac isoforms.
Haeusler
Lars Christian
LC
Max-Planck-Institute of Molecular Physiology, Department of Structural Biology, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
Blumenstein
Lars
L
Stege
Patricia
P
Dvorsky
Radovan
R
Ahmadian
Mohammad Reza
MR
D020816:Amino Acid Motifs; D017124:Conserved Sequence; D004789:Enzyme Activation / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D020662:Guanine Nucleotide Exchange Factors; D007527:Isoenzymes; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein