title: Cotranslational folding of spectrin domains via partially structured states.
abstract: How do the key features of protein folding, elucidated from studies on native, isolated proteins, manifest in cotranslational folding on the ribosome? Using a well-characterized family of homologous α-helical proteins with a range of biophysical properties, we show that spectrin domains can fold vectorially on the ribosome and may do so via a pathway different from that of the isolated domain. We use cryo-EM to reveal a folded or partially folded structure, formed in the vestibule of the ribosome. Our results reveal that it is not possible to predict which domains will fold within the ribosome on the basis of the folding behavior of isolated domains; instead, we propose that a complex balance of the rate of folding, the rate of translation and the lifetime of folded or partly folded states will determine whether folding occurs cotranslationally on actively translating ribosomes.
authors.affiliation: Department of Biochemistry and Biophysics Stockholm University, Stockholm, Sweden.
authors.forename: Ola B
authors.initials: OB
authors.lastname: Nilsson
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Nickson
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hollins
authors.affiliation: Gene Center and Center for Integrated Protein Science Munich (CiPS-M), University of Munich, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wickles
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Annette
authors.initials: A
authors.lastname: Steward
authors.affiliation: Gene Center and Center for Integrated Protein Science Munich (CiPS-M), University of Munich, Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Beckmann
authors.affiliation: Department of Biochemistry and Biophysics Stockholm University, Stockholm, Sweden.|Science for Life Laboratory, Stockholm University, Solna, Sweden.
authors.forename: Gunnar
authors.identifier: 0000-0002-4490-8569
authors.initials: G
authors.lastname: von Heijne
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Clarke
mesh_terms: D000595:Amino Acid Sequence; D001696:Biomechanical Phenomena; D020285:Cryoelectron Microscopy; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D014176:Protein Biosynthesis; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D013049:Spectrin