title: A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium.
abstract: The Rho family of small GTPases represent well characterized signaling molecules that regulate many cellular functions such as actin cytoskeletal arrangement and the cell cycle by acting as molecular switches. A Rac1-GDP-Zn complex has been crystallized in space group P3(2)21 and its crystal structure has been solved at 1.9 A resolution. These trigonal crystals reveal the unexpected ability of Rac1 to coordinate Zn atoms in a tetrahedral fashion by use of its biologically relevant switch I and switch II regions. Upon coordination of zinc, the switch I region is stabilized in the GDP-bound conformation and contributes to a Rac1 trimer in the asymmetric unit. Zinc coordination causes switch II to adopt a novel conformation with a symmetry-related molecule. Additionally, zinc was found to displace magnesium from its octahedral coordination at switch I, although GDP binding remained stable. This structure represents the first reported Rac1-GDP-Zn complex, which further underscores the conformational flexibility and versatility of the small GTPase switch regions.
authors: Laboratory of Structural Microbiology, Rockefeller University, New York, NY 10021, USA.
authors: Gerd
authors: G
authors: Prehna
authors: C Erec
authors: CE
authors: Stebbins
mesh_terms: D001704:Biopolymers / Q000737:chemistry*; D003460:Crystallization; D006153:Guanosine Diphosphate / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D015032:Zinc / Q000737:chemistry*; D020830:rac1 GTP-Binding Protein / Q000737:chemistry*
chemical_list: D001704:Biopolymers; D006153:Guanosine Diphosphate; D020830:rac1 GTP-Binding Protein; D008274:Magnesium; D015032:Zinc