TY - JOUR
T1 - Dynamic Behavior of Trigger Factor on the Ribosome
AU - Deeng, J.
AU - Chan, K. Y.
AU - van der Sluis, E. O.
AU - Berninghausen, O.
AU - Han, W.
AU - Gumbart, J.
AU - Schulten, K.
AU - Beatrix, B.
AU - Beckmann, R.
N1 - This work was supported by grants of the Deutsche Forschungsgemeinschaft, SFB594 (to R.B. and B.B.), CIPSM (to R.B.), FOR967 (to R.B.), an advanced investigator grant of the ERC CRYOTRANSLATION (to R.B.), a scholarship of the IMPRIS-LS to J.D. and the Genecenter cryo-EM facility. This work was also supported by grants from the National Institutes of Health (9P41GM104601) and the National Science Foundation (PHY0822613). Computer time on Stampede at the Texas Advanced Computing Center (TACC) was provided by grant MCA93S028 from the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number OCI-1053575. This research is also part of the Blue Waters Early Science project, which is supported by the National Science Foundation (award number OCI 07-25070) and the state of Illinois.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/9/11
Y1 - 2016/9/11
N2 - Trigger factor (TF) is the only ribosome-associated chaperone in bacteria. It interacts with hydrophobic segments in nascent chain (NCs) as they emerge from the ribosome. TF binds via its N-terminal ribosome-binding domain (RBD) mainly to ribosomal protein uL23 at the tunnel exit on the large ribosomal subunit. Whereas earlier structural data suggested that TF binds as a rigid molecule to the ribosome, recent comparisons of structural data on substrate-bound, ribosome-bound, and TF in solution from different species suggest that this chaperone is a rather flexible molecule. Here, we present two cryo-electron microscopy structures of TF bound to ribosomes translating an mRNA coding for a known TF substrate from Escherichia coli of a different length. The structures reveal distinct degrees of flexibility for the different TF domains, a conformational rearrangement of the RBD upon ribosome binding, and an increase in rigidity within TF when the NC is extended. Molecular dynamics simulations agree with these data and offer a molecular basis for these observations.
AB - Trigger factor (TF) is the only ribosome-associated chaperone in bacteria. It interacts with hydrophobic segments in nascent chain (NCs) as they emerge from the ribosome. TF binds via its N-terminal ribosome-binding domain (RBD) mainly to ribosomal protein uL23 at the tunnel exit on the large ribosomal subunit. Whereas earlier structural data suggested that TF binds as a rigid molecule to the ribosome, recent comparisons of structural data on substrate-bound, ribosome-bound, and TF in solution from different species suggest that this chaperone is a rather flexible molecule. Here, we present two cryo-electron microscopy structures of TF bound to ribosomes translating an mRNA coding for a known TF substrate from Escherichia coli of a different length. The structures reveal distinct degrees of flexibility for the different TF domains, a conformational rearrangement of the RBD upon ribosome binding, and an increase in rigidity within TF when the NC is extended. Molecular dynamics simulations agree with these data and offer a molecular basis for these observations.
KW - chaperones
KW - cryo-electron microscopy
KW - molecular dynamics simulation
KW - protein folding
KW - ribosome-binding domain
UR - https://www.scopus.com/pages/publications/84977631164
UR - https://www.sciencedirect.com/science/article/abs/pii/S0022283616302157?via%3Dihub
U2 - 10.1016/j.jmb.2016.06.007
DO - 10.1016/j.jmb.2016.06.007
M3 - Journal article
C2 - 27320387
AN - SCOPUS:84977631164
SN - 0022-2836
VL - 428
SP - 3588
EP - 3602
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 18
ER -
SDG 3 Good Health and Well-being