Transient tether between the SRP RNA and SRP receptor ensures efficient cargo delivery during cotranslational protein targeting.
Kinetic control of macromolecular interactions plays key roles in biological regulation. An example of such control occurs in cotranslational protein targeting by the signal recognition particle (SRP), during which the SRP RNA and the cargo both accelerate complex assembly between the SRP and SRP receptor FtsY 10(2)-fold. The molecular mechanism underlying these rate accelerations was unclear. Here we show that a highly conserved basic residue, Lys399, on the lateral surface of FtsY provides a novel RNA tetraloop receptor to mediate the SRP RNA- and cargo-induced acceleration of SRP-FtsY complex assembly. We propose that the SRP RNA, by using its tetraloop to interact with FtsY-Lys399, provides a transient tether to stabilize the early stage and transition state of complex formation; this accelerates the assembly of a stable SRP-FtsY complex and allows the loading of cargo to be efficiently coupled to its membrane delivery. The use of a transient tether to increase the lifetime of collisional intermediates and reduce the dimension of diffusional search represents a novel and effective mechanism to accelerate macromolecular interactions.
Shen
Kuang
K
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, CA 91125, USA.
Shan
Shu-ou
SO
D000595:Amino Acid Sequence; D029681:Arabidopsis Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D060365:Chloroplast Proteins; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D005453:Fluorescence; D008565:Membrane Proteins / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011388:Prolactin; D011498:Protein Precursors; D021381:Protein Transport / Q000502:physiology; D012313:RNA / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D018271:Signal Recognition Particle / Q000737:chemistry / Q000378:metabolism*; D013045:Species Specificity; D055672:Static Electricity
D029681:Arabidopsis Proteins; D001426:Bacterial Proteins; D060365:Chloroplast Proteins; D029968:Escherichia coli Proteins; C082931:Ffh protein, E coli; C087406:FtsY protein, Bacteria; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011498:Protein Precursors; D018160:Receptors, Cytoplasmic and Nuclear; D018271:Signal Recognition Particle; C513946:cpFtsY protein, Arabidopsis; D012313:RNA; C017671:preprolactin; D011388:Prolactin
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