title: Direct visualization reveals dynamics of a transient intermediate during protein assembly.
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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Vinh Q
authors.initials: VQ
authors.lastname: Lam
authors.forename: Yun
authors.initials: Y
authors.lastname: Mou
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Kimura
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Chung
authors.forename: Sowmya
authors.initials: S
authors.lastname: Chandrasekar
authors.forename: Jay R
authors.initials: JR
authors.lastname: Winkler
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Mayo
authors.forename: Shu-ou
authors.initials: SO
authors.lastname: Shan
mesh_terms: D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C409968:4.5S RNA; D029968:Escherichia coli Proteins; C082931:Ffh protein, E coli; D012329:RNA, Bacterial; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018271:Signal Recognition Particle; C036318:signal peptide receptor