Title: Trajectories of the ribosome as a Brownian nanomachine

Abstract

In a Brownian machine, there is a tiny device buffeted by the random motions of molecules in the environment, is capable of exploiting these thermal motions for many of the conformational changes in its work cycle. Such machines are now thought to be ubiquitous, with the ribosome, a molecular machine responsible for protein synthesis, increasingly regarded as prototypical. We present a new analytical approach capable of determining the free-energy landscape and the continuous trajectories of molecular machines from a large number of snapshots obtained by cryogenic electron microscopy. We demonstrate this approach in the context of experimental cryogenic electron microscope images of a large ensemble of nontranslating ribosomes purified from yeast cells. The free-energy landscape is seen to contain a closed path of low energy, along which the ribosome exhibits conformational changes known to be associated with the elongation cycle. This approach allows model-free quantitative analysis of the degrees of freedom and the energy landscape underlying continuous conformational changes in nanomachines, including those important for biological function.

Authors:

Dashti, Ali; Schwander, Peter; Langlois, Robert; Fung, Russell; Li, Wen; Hosseinizadeh, Ahmad; Liao, Hstau Y.; Pallesen, Jesper; Sharma, Gyanesh; Stupina, Vera A.; Simon, Anne E.; Dinman, Jonathan D.; Frank, Joachim; Ourmazd, Abbas

Publication Date:

Mon Nov 24 00:00:00 EST 2014

Research Org.:

Univ. of Wisconsin, Milwaukee, WI (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Science Foundation (NSF)

OSTI Identifier:

1235098

Alternate Identifier(s):

OSTI ID: 1356190

Grant/Contract Number:  

FG02-09ER16114; SC0002164; R01 GM29169; GM55440; 1157906

Resource Type:

Published Article

Journal Name:

Proceedings of the National Academy of Sciences of the United States of America

Additional Journal Information:

Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 111 Journal Issue: 49; Journal ID: ISSN 0027-8424

Publisher:

Proceedings of the National Academy of Sciences

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; cryo-electron microscopy; elongation cycle; manifold embedding; nanomachines; translation