PMID:21464281

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Citation

Zhang, X, Lam, VQ, Mou, Y, Kimura, T, Chung, J, Chandrasekar, S, Winkler, JR, Mayo, SL and Shan, SO (2011) Direct visualization reveals dynamics of a transient intermediate during protein assembly. Proc. Natl. Acad. Sci. U.S.A. 108:6450-5

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.

Links

PubMed PMC3081034 Online version:10.1073/pnas.1019051108

Keywords

Escherichia coli/chemistry; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Protein Structure, Quaternary; RNA, Bacterial/chemistry; RNA, Bacterial/genetics; RNA, Bacterial/metabolism; Receptors, Cytoplasmic and Nuclear/chemistry; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Peptide/chemistry; Receptors, Peptide/genetics; Receptors, Peptide/metabolism; Signal Recognition Particle/chemistry; Signal Recognition Particle/genetics; Signal Recognition Particle/metabolism

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