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Direct Visualization Reveals Dynamics of a Transient Intermediate During Protein Assembly

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Multistate GTPase Control Co-translational Protein Targeting

Part of the book series: Springer Theses ((Springer Theses))

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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 stable complexes. However, the nature and roles of these transient intermediates remain elusive. Here, we characterized the structural, dynamic, and energetic properties of a transient, on-pathway intermediate during complex assembly between the signal recognition particle (SRP) and its receptor (SR). We show that this intermediate has an overlapping but distinct interaction interface from that of the final complex, and 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 provide a framework for understanding the role of transient intermediates in protein assembly and biological regulation.

A version of this chapter has been published as Zhang X, Lam VQ, Mou Y, Kimura T, Chung J, Chandrasekar S, Winkler JR, Mayo SL, Shan S (2011) Direct visualization reveals dynamics of a transient intermediate during protein assembly. Proc Natl Acad Sci U S A 108:6450–6455

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Acknowledgment

Electron paramagnetic (EPR) measurements were carried out by Dr. Vinh Q. Lam; molecular docking and Brownian Dynamics simulations were carried out by Yun Mou and Dr. Steven L. Mayo; time-resolved FRET (TR-FRET) measurements were assisted by Dr. Tetsunari Kimura and Dr. Jay R. Winkler; sequence alignment was performed by Sowmya Chandrasekar. We thank 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 NIH grants GM078024 to S.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.S.

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  1. The Scripps Research Institute, North Torrey Pines Rd 10550, Mail Stop: BCC265, La Jolla, CA, 92037, USA

    Xin Zhang

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Correspondence to Xin Zhang .

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Zhang, X. (2012). Direct Visualization Reveals Dynamics of a Transient Intermediate During Protein Assembly. In: Multistate GTPase Control Co-translational Protein Targeting. Springer Theses. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7808-0_3

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