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The ribosome modulates nascent protein folding.


ABSTRACT: Proteins are synthesized by the ribosome and generally must fold to become functionally active. Although it is commonly assumed that the ribosome affects the folding process, this idea has been extremely difficult to demonstrate. We have developed an experimental system to investigate the folding of single ribosome-bound stalled nascent polypeptides with optical tweezers. In T4 lysozyme, synthesized in a reconstituted in vitro translation system, the ribosome slows the formation of stable tertiary interactions and the attainment of the native state relative to the free protein. Incomplete T4 lysozyme polypeptides misfold and aggregate when free in solution, but they remain folding-competent near the ribosomal surface. Altogether, our results suggest that the ribosome not only decodes the genetic information and synthesizes polypeptides, but also promotes efficient de novo attainment of the native state.

SUBMITTER: Kaiser CM 

PROVIDER: S-EPMC4172366 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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The ribosome modulates nascent protein folding.

Kaiser Christian M CM   Goldman Daniel H DH   Chodera John D JD   Tinoco Ignacio I   Bustamante Carlos C  

Science (New York, N.Y.) 20111201 6063


Proteins are synthesized by the ribosome and generally must fold to become functionally active. Although it is commonly assumed that the ribosome affects the folding process, this idea has been extremely difficult to demonstrate. We have developed an experimental system to investigate the folding of single ribosome-bound stalled nascent polypeptides with optical tweezers. In T4 lysozyme, synthesized in a reconstituted in vitro translation system, the ribosome slows the formation of stable tertia  ...[more]

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