title: Heterodimeric GTPase core of the SRP targeting complex.
abstract: Two structurally homologous guanosine triphosphatase (GTPase) domains interact directly during signal recognition particle (SRP)-mediated cotranslational targeting of proteins to the membrane. The 2.05 angstrom structure of a complex of the NG GTPase domains of Ffh and FtsY reveals a remarkably symmetric heterodimer sequestering a composite active site that contains two bound nucleotides. The structure explains the coordinate activation of the two GTPases. Conformational changes coupled to formation of their extensive interface may function allosterically to signal formation of the targeting complex to the signal-sequence binding site and the translocon. We propose that the complex represents a molecular "latch" and that its disengagement is regulated by completion of assembly of the GTPase active site.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Focia
authors.forename: Irina V
authors.initials: IV
authors.lastname: Shepotinovskaya
authors.forename: James A
authors.initials: JA
authors.lastname: Seidler
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Freymann
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000378:metabolism; D013824:Thermus / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; C087406:FtsY protein, Bacteria; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D018271:Signal Recognition Particle; C004805:5'-guanylylmethylenebisphosphonate; D006160:Guanosine Triphosphate; D020962:Heterotrimeric GTP-Binding Proteins