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Published April 27, 2010 | Published + Supplemental Material
Journal Article Open

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.

Additional Information

© 2010 the National Academy of Sciences. Freely available online through the PNAS open access option. Communicated by Douglas C. Rees, Caltech/Howard Hughes Medical Institute, Pasadena, CA, March 16, 2010 (received for review October 9, 2009). Published online before print April 12, 2010. We thank William M. Clemons, Nenad Ban, Christiane Schaffitzel, and members of the Shan group for helpful comments on the manuscript. This work was supported by National Institutes of Health Grant GM078024 (S.S.). S.S. was supported by a career award from the Burroughs Welcome Foundation, the Beckman Young Investigator award, the Packard and Lucile Award in Science and Engineering, and the Henry Dreyfus Teacher- Scholar Award. Author contributions: K.S. and S.-o.S. designed research; K.S. performed research; K.S. analyzed data; and K.S. and S.-o.S. wrote the paper.

Attached Files

Published - Shen2010p10034P_Natl_Acad_Sci_Usa.pdf

Supplemental Material - pnas.1002968107_SI.pdf


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