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Direct visualization reveals dynamics of a transient intermediate during protein assembly

Zhang, Xin and Lam, Vinh Q. and Mou, Yun and Kimura, Tetsunari and Chung, Jaeyoon and Chandrasekar, Sowmya and Winkler, Jay R. and Mayo, Stephen L. and Shan, Shu-ou (2011) Direct visualization reveals dynamics of a transient intermediate during protein assembly. Proceedings of the National Academy of Sciences of the United States of America, 108 (16). pp. 6450-6455. ISSN 0027-8424. PMCID PMC3081034. http://resolver.caltech.edu/CaltechAUTHORS:20110511-090620791

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1019051108 DOIArticle
http://www.pnas.org/content/108/16/6450PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081034/PubMed CentralArticle
ORCID:
AuthorORCID
Shan, Shu-ou0000-0002-6526-1733
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.
Funders:
Funding AgencyGrant Number
NIHGM078024
NIHGM068041
Burroughs Welcome Foundation UNSPECIFIED
Camille and Henry Dreyfus FoundationUNSPECIFIED
Arnold and Mabel Beckman Foundation UNSPECIFIED
David and Lucile Packard Foundation UNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)UNSPECIFIED
Subject Keywords:EPR spectroscopy; fluorescence spectroscopy; molecular recognition; protein targeting; GTPases
PubMed Central ID:PMC3081034
Record Number:CaltechAUTHORS:20110511-090620791
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20110511-090620791
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:23632
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 May 2011 16:27
Last Modified:31 Jan 2017 19:07

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