Co-translational protein targeting by the signal recognition particle.
The signal recognition particle (SRP) mediates the co-translational targeting of nascent proteins to the eukaryotic endoplasmic reticulum membrane, or the bacterial plasma membrane. During this process, two GTPases, one in the SRP and one in the SRP receptor (SR), form a complex in which both proteins reciprocally activate the GTPase reaction of one another. The recent crystal structures of the T. aquaticus SRP.SR complex show that the two GTPases associate via an unusually extensive and highly cooperative interaction surface, and form a composite active site at the interface. GTPase activation proceeds through a unique mechanism, stimulated by both interactions between the twinned GTP molecules across the dimer interface and by conformational rearrangements that position catalytic residues in each active site with respect to the bound substrates. Distinct classes of mutations have been isolated that inhibit specific stages during SRP-SR complex formation and activation, suggesting discrete conformational stages during formation of the active SRP.SR complex. Each stage provides a potential control point in the targeting reaction at which regulation by additional components can be exerted, thus ensuring the binding and release of cargo at the appropriate time.
Shan
Shu-ou
SO
Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, USA.
Walter
Peter
P
D001426:Bacterial Proteins / Q000378:metabolism*; D003461:Crystallography; D029968:Escherichia coli Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008958:Models, Molecular; D014176:Protein Biosynthesis; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000378:metabolism* / Q000502:physiology*
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C082931:Ffh protein, E coli; C087406:FtsY protein, Bacteria; D018160:Receptors, Cytoplasmic and Nuclear; D018271:Signal Recognition Particle; D020558:GTP Phosphohydrolases