X-ray structures of the signal recognition particle receptor reveal targeting cycle intermediates.
The signal recognition particle (SRP) and its conjugate receptor (SR) mediate cotranslational targeting of a subclass of proteins destined for secretion to the endoplasmic reticulum membrane in eukaryotes or to the plasma membrane in prokaryotes. Conserved active site residues in the GTPase domains of both SRP and SR mediate discrete conformational changes during formation and dissociation of the SRP.SR complex. Here, we describe structures of the prokaryotic SR, FtsY, as an apo protein and in two different complexes with a non-hydrolysable GTP analog (GMPPNP). These structures reveal intermediate conformations of FtsY containing GMPPNP and explain how the conserved active site residues position the nucleotide into a non-catalytic conformation. The basis for the lower specificity of binding of nucleotide in FtsY prior to heterodimerization with the SRP conjugate Ffh is also shown. We propose that these structural changes represent discrete conformational states assumed by FtsY during targeting complex formation and dissociation.
Reyes
Christopher L
CL
Graduate Group in Biophysics, Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California, United States of America.
Rutenber
Earl
E
Walter
Peter
P
Stroud
Robert M
RM
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002453:Cell Cycle / Q000502:physiology*; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D009711:Nucleotides / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018271:Signal Recognition Particle / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013824:Thermus / Q000378:metabolism
D001426:Bacterial Proteins; C087406:FtsY protein, Bacteria; D009711:Nucleotides; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018271:Signal Recognition Particle; C036318:signal peptide receptor; D006165:Guanylyl Imidodiphosphate; D020558:GTP Phosphohydrolases