Structures of Trichomonas vaginalis macrophage migratory inhibitory factor
-
1.
California Institute of Technology
-
2.
University of Washington
-
3.
New York Structural Biology Center
-
4.
University of Fribourg
Abstract
The unicellular parasitic protozoan Trichomonas vaginalis causes trichomoniasis, the most prevalent nonviral sexually transmitted disease globally. T. vaginalis evades host immune responses by producing homologs of host proteins, including cytokines such as macrophage migration inhibitory factor. T. vaginalis macrophage migration inhibitory factor (TvMIF) helps to facilitate the survival of T. vaginalis during nutritional stress conditions, increases prostate cell proliferation and invasiveness, and induces inflammation-related cellular pathways, thus mimicking the ability of human MIF to increase inflammation and cell proliferation. The production, crystallization and three structures of N-terminally hexahistidine-tagged TvMIF reveal a prototypical MIF trimer with a topology similar to that of human homologs (hMIF-1 and hMIF-2). The N-terminal tag obscures the expected pyruvate-binding site. The similarity of TvMIF to its human homologs can be exploited for structure-based drug discovery.
Copyright and License
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Funding
This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Contract No. 75N93022C00036.
Acknowledgement
This project is part of an SSGCID collaboration led by OAA to train diverse students in structural science, rational structure-based drug discovery and scientific communication. This project piloted the feasibility of expanding the training virtually with a biochemist, Dr Rabih Darwiche, and high-school student volunteers. AAS is a freshman at Caltech and a Grafton High alumna. AN is a sophomore at Reedy High, Texas. OCOD and RG are seniors at Grafton High School, Virginia. We are grateful for the support of the Dartmouth Cancer Center Director, Dr Steven Leach, and the Dartmouth Cancer Center Office of Diversity Equity, Inclusion and Belonging. This research used resources from the NYX beamline 19-ID, supported by the New York Structural Biology Center, at the National Synchrotron Light Source II, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under Contract No. DE-SC0012704. The NYX detector instrumentation was supported by grant S10OD030394 through the Office of the Director of the National Institutes of Health.
Supplemental Material
Supporting information:
- 3D view
- PDB references: macrophage migration inhibitory factor, I41, 8ur2; space group I4122, 8ur4; space group P41212, 8uz4
- Supplementary Figures. DOI: https://doi.org/10.1107/S2053230X24011105/ir5039sup1.pdf
Files
| Name | Size | Download all |
|---|---|---|
|
md5:ee7b10edd4056bc97fb9225d3285201e
|
13.7 MB | Preview Download |
|
md5:eb6f3af502453a274512dc7b21579cc1
|
1.7 MB | Preview Download |
Additional details
- National Institute of Allergy and Infectious Diseases
- 75N93022C00036
- Accepted
-
2024-11-14Accepted
- Available
-
2024-11-27Published online
- Caltech groups
- Division of Biology and Biological Engineering
- Publication Status
- Published