Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published April 19, 2011 | Published + Supplemental Material
Journal Article Open

Direct visualization reveals dynamics of a transient intermediate during protein assembly


Interactions between proteins underlie numerous biological functions. Theoretical work suggests that protein interactions initiate with formation of transient intermediates that subsequently relax to specific, stable complexes. However, the nature and roles of these transient intermediates have remained elusive. Here, we characterized the global structure, dynamics, and stability of a transient, on-pathway intermediate during complex assembly between the Signal Recognition Particle (SRP) and its receptor. We show that this intermediate has overlapping but distinct interaction interfaces from that of the final complex, and it is stabilized by long-range electrostatic interactions. A wide distribution of conformations is explored by the intermediate; this distribution becomes more restricted in the final complex and is further regulated by the cargo of SRP. These results suggest a funnel-shaped energy landscape for protein interactions, and they provide a framework for understanding the role of transient intermediates in protein assembly and biological regulation.

Additional Information

© 2011 National Academy of Sciences. Edited by José N. Onuchic, University of California, San Diego, La Jolla, CA, and approved February 25, 2011 (received for review December 17, 2010). Published online before print April 4, 2011. We thank B.S.P. Araujo for modeling the effect of fluorophore linkers on distant measurements; H.B. Gray and P.E. Wright for insightful discussions; and D.C. Rees, T.F. Miller III, and members of the Shan laboratory for comments on the manuscript. This work was supported by National Institutes of Health Grants GM078024 to S.-o.S. and GM068041 to J.R.W., DARPA Protein Design Processes to S.L.M., and career awards from the Burroughs Welcome Foundation, the Henry and Camille Dreyfus Foundation, the Arnold and Mabel Beckman Foundation, and the David and Lucile Packard Foundation to S.-o.S. Author contributions: X.Z., V.Q.L., J.R.W., and S.-o.S. designed research; X.Z., V.Q.L., Y.M., T.K., J.C., S.C., and S.-o.S. performed research; X.Z. and V.Q.L. contributed new reagents/analytic tools; X.Z., V.Q.L., Y.M., T.K., J.R.W., S.L.M., and S.-o.S. analyzed data; and X.Z. and S.-o.S. wrote the paper.

Attached Files

Published - Zhang2011p13713P_Natl_Acad_Sci_Usa.pdf

Supplemental Material - SM01.mov

Supplemental Material - pnas.1019051108_SI.pdf


Files (14.4 MB)
Name Size Download all
1.5 MB Preview Download
2.8 MB Preview Download
10.2 MB Download

Additional details

August 22, 2023
October 23, 2023