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Biochemistry Seminar/ Reinhart Seminar Series- Dr. Carlos Bustamante: “Co-translational Protein Folding One Molecular at a Time””

October 9 @ 4:00 pm - 5:00 pm

Reinhart seminar series

UC Berekeley/Howard Hughes Med. Inst.

Host: Hays Rye

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 optical tweezers to investigate the folding of single ribosome-bound stalled nascent polypeptides of T4 lysozyme synthesized in a reconstituted in vitro translation system. Significantly, we find that 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. These 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. On the other hand, interactions between the nascent polypeptide and the ribosome exit tunnel represent one mode of regulating synthesis rates. The SecM protein arrests its own translation, and release of arrest at the translocon has been proposed to occur by mechanical force. Using optical tweezers, we demonstrate that arrest of SecM-stalled ribosomes can indeed be rescued by force alone and that the force needed to release stalling can be generated in vivo by a nascent chain folding near the ribosome tunnel exit. We formulate a kinetic model describing how a protein can regulate its own synthesis by the force generated during folding, tuning ribosome activity to structure acquisition by a nascent polypeptide.

Details

Date:
October 9
Time:
4:00 pm - 5:00 pm
Event Category:

Organizer

Hays Rye

Venue

108 Biochemistry Building (Bldg.#1507)
300 Olsen Blvd
College Station, TX 77845 United States
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