Protein folding. Translational tuning optimizes nascent protein folding in cells.

Autor: Kim SJ; Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA., Yoon JS; Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA., Shishido H; Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA., Yang Z; Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA., Rooney LA; Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA., Barral JM; Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77550-0620, USA. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77550-0620, USA., Skach WR; Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA. Cystic Fibrosis Foundation Therapeutics, Bethesda, MD 20814, USA. skachw@ohsu.edu.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2015 Apr 24; Vol. 348 (6233), pp. 444-8.
DOI: 10.1126/science.aaa3974
Abstrakt: In cells, biosynthetic machinery coordinates protein synthesis and folding to optimize efficiency and minimize off-pathway outcomes. However, it has been difficult to delineate experimentally the mechanisms responsible. Using fluorescence resonance energy transfer, we studied cotranslational folding of the first nucleotide-binding domain from the cystic fibrosis transmembrane conductance regulator. During synthesis, folding occurred discretely via sequential compaction of N-terminal, α-helical, and α/β-core subdomains. Moreover, the timing of these events was critical; premature α-subdomain folding prevented subsequent core formation. This process was facilitated by modulating intrinsic folding propensity in three distinct ways: delaying α-subdomain compaction, facilitating β-strand intercalation, and optimizing translation kinetics via codon usage. Thus, de novo folding is translationally tuned by an integrated cellular response that shapes the cotranslational folding landscape at critical stages of synthesis.
(Copyright © 2015, American Association for the Advancement of Science.)
Databáze: MEDLINE
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