Transmembrane but not soluble helices fold inside the ribosome tunnel
Nascent peptide harbouring VSV TM segment within the ribosome exit tunnel. The nascent peptide is shown in cartoon representation (orange) bound to tRNA (yellow). Ribosomal proteins are shown in a surface representation and colored by residue type: (white) hydrophobic, (green) polar, and (blue) positively charged. Ribosomal RNA is also shown in a surface representation and colored gray.
Bano-Polo M, Baeza-Delgado C, Tamborero S, Hazel A, Grau B, Nilsson I, Whitley P, Gumbart JC, von Heijne G, Mingarro I.
Nat Commun 2018 Dec; 9: 5246.
Integral membrane proteins are assembled into the ER membrane via a continuous ribosome-translocon channel. The hydrophobicity and thickness of the core of the membrane bilayer leads to the expectation that transmembrane (TM) segments minimize the cost of harbouring polar polypeptide backbones by adopting a regular pattern of hydrogen bonds to form alpha-helices before integration. Co-translational folding of nascent chains into an alpha-helical conformation in the ribosomal tunnel has been demonstrated previously, but the features governing this folding are not well understood. In particular, little is known about what features influence the propensity to acquire alpha-helical structure in the ribosome. Using in vitro translation of truncated nascent chains trapped within the ribosome tunnel and molecular dynamics simulations, we show that folding in the ribosome is attained for TM helices but not for soluble helices, presumably facilitating SRP (signal recognition particle) recognition and/or a favourable conformation for membrane integration upon translocon entry.
PubMed: 30531789. Doi: 10.1038/s41467-018-07554-7. Free PMC article
