|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Science / Faculty of Science >
Peer-reviewed Journal Articles, etc >
Structural insight into proline cis/trans isomerization of unfolded proteins catalyzed by the trigger factor chaperone
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Structural insight into proline cis/trans isomerization of unfolded proteins catalyzed by the trigger factor chaperone |
| Authors: | Kawagoe, Soichiro Browse this author | | Nakagawa, Hiroshi Browse this author | | Kumeta, Hiroyuki Browse this author | | Ishimori, Koichiro Browse this author →KAKEN DB | | Saio, Tomohide Browse this author →KAKEN DB |
| Keywords: | molecular chaperone | | prolyl isomerase | | molecular dynamics | | protein folding | | structure-function | | nuclear magnetic resonance (NMR) | | hydrophobic interaction | | peptidyl-prolyl isomerase domain | | trigger factor |
| Issue Date: | 28-Sep-2018 |
| Publisher: | American Society for Biochemistry and Molecular Biology (ASBMB) |
| Journal Title: | Journal of Biological Chemistry (JBC) |
| Volume: | 293 |
| Issue: | 39 |
| Start Page: | 15095 |
| End Page: | 15106 |
| Publisher DOI: | 10.1074/jbc.RA118.003579 |
| Abstract: | Molecular chaperones often possess functional modules that are specialized in assisting the formation of specific structural elements, such as a disulfide bridges and peptidyl-prolyl bonds in cis form, in the client protein. A ribosome-associated molecular chaperone trigger factor (TF), which has a peptidyl-prolyl cis/trans isomerase (PPIase) domain, acts as a highly efficient catalyst in the folding process limited by peptidyl-prolyl isomerization. Herein we report a study on the mechanism through which TF recognizes the proline residue in the unfolded client protein during the cis/trans isomerization process. The solution structure of TF in complex with the client protein showed that TF recognizes the proline-aromatic motif located in the hydrophobic stretch of the unfolded client protein through its conserved hydrophobic cleft, which suggests that TF preferentially accelerates the isomerization of the peptidyl-prolyl bond that is eventually folded into the core of the protein in its native fold. Molecular dynamics simulation revealed that TF exploits the backbone amide group of Ile(195) to form an intermolecular hydrogen bond with the carbonyl oxygen of the amino acid residue preceding the proline residue at the transition state, which presumably stabilizes the transition state and thus accelerates the isomerization. The importance of such intermolecular hydrogen-bond formation during the catalysis was further corroborated by the activity assay and NMR relaxation analysis. |
| Rights: | This research was originally published in the Journal of Biological Chemistry. Authors. Soichiro Kawagoe, Hiroshi Nakagawa, Hiroyuki Kumeta, Koichiro Ishimori and Tomohide SaioTitle. J. Biol. Chem. 2018; Vol. 293, No. 39 : pp15095-pp15106. © 2018 Kawagoe et al. | | http://creativecommons.org/licenses/by/4.0 |
| Type: | article |
| URI: | http://hdl.handle.net/2115/73070 |
| Appears in Collections: | 理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 齋尾 智英
|
