title: Cotranslational Protein Folding inside the Ribosome Exit Tunnel.
abstract: At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins.
authors: Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 106 91 Stockholm, Sweden.
authors: Ola B
authors: OB
authors: Nilsson
authors: Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 106 91 Stockholm, Sweden.
authors: Rickard
authors: R
authors: Hedman
authors: Gene Center and Center for Integrated Protein Science Munich, CiPS-M, Feodor-Lynen-Strasse 25, University of Munich, 81377 Munich, Germany.
authors: Jacopo
authors: J
authors: Marino
authors: Gene Center and Center for Integrated Protein Science Munich, CiPS-M, Feodor-Lynen-Strasse 25, University of Munich, 81377 Munich, Germany.
authors: Stephan
authors: S
authors: Wickles
authors: Gene Center and Center for Integrated Protein Science Munich, CiPS-M, Feodor-Lynen-Strasse 25, University of Munich, 81377 Munich, Germany.
authors: Lukas
authors: L
authors: Bischoff
authors: Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Box 596, 751 24 Uppsala, Sweden.
authors: Magnus
authors: M
authors: Johansson
authors: Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 106 91 Stockholm, Sweden.
authors: Annika
authors: A
authors: Müller-Lucks
authors: Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
authors: Fabio
authors: F
authors: Trovato
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA; Stanford Magnetic Resonance Laboratory, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.
authors: Joseph D
authors: JD
authors: Puglisi
authors: Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
authors: Edward P
authors: EP
authors: O'Brien
authors: Gene Center and Center for Integrated Protein Science Munich, CiPS-M, Feodor-Lynen-Strasse 25, University of Munich, 81377 Munich, Germany.
authors: Roland
authors: R
authors: Beckmann
authors: Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 106 91 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, Box 1031, 171 21 Solna, Sweden. Electronic address: gunnar@dbb.su.se.
authors: Gunnar
authors: G
authors: von Heijne
mesh_terms: D020285:Cryoelectron Microscopy; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D005656:Fungal Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D014176:Protein Biosynthesis; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry; D013816:Thermodynamics; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; C497347:SecM protein, E coli; D014157:Transcription Factors