title: A structural ensemble of a ribosome-nascent chain complex during cotranslational protein folding.
abstract: Although detailed pictures of ribosome structures are emerging, little is known about the structural and cotranslational folding properties of nascent polypeptide chains at the atomic level. Here we used solution-state NMR spectroscopy to define a structural ensemble of a ribosome-nascent chain complex (RNC) formed during protein biosynthesis in Escherichia coli, in which a pair of immunoglobulin-like domains adopts a folded N-terminal domain (FLN5) and a disordered but compact C-terminal domain (FLN6). To study how FLN5 acquires its native structure cotranslationally, we progressively shortened the RNC constructs. We found that the ribosome modulates the folding process, because the complete sequence of FLN5 emerged well beyond the tunnel before acquiring native structure, whereas FLN5 in isolation folded spontaneously, even when truncated. This finding suggests that regulating structure acquisition during biosynthesis can reduce the probability of misfolding, particularly of homologous domains.
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Cabrita
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: AnaÏs M E
authors.initials: AME
authors.lastname: Cassaignau
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Helene M M
authors.initials: HMM
authors.lastname: Launay
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Waudby
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wlodarski
authors.affiliation: institute of Structural and Molecular Biology, University College London.
authors.forename: Carlo
authors.initials: C
authors.lastname: Camilloni
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Maria-Evangelia
authors.initials: ME
authors.lastname: Karyadi
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Robertson
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Wentink
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Goodsell
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Woolhead
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge United Kingdom.
authors.forename: Michele
authors.initials: M
authors.lastname: Vendruscolo
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.affiliation: institute of Structural and Molecular Biology, University College London.|School of Crystallography, Birkbeck College, University of London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D014176:Protein Biosynthesis; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins