التفاصيل البيبلوغرافية
| العنوان: |
Structure and Function of the Dot/Icm T4SS |
| المؤلفون: |
Dutka, Przemysław, Liu, Yuxi, Maggi, Stefano, Ghosal, Debnath, Wang, Jue, Carter, Stephen D., Zhao, Wei, Vijayrajratnam, Sukhithasri, Vogel, Joseph P., Jensen, Grant J. |
| سنة النشر: |
2023 |
| المجموعة: |
Caltech Authors (California Institute of Technology) |
| الوصف: |
The Legionella pneumophila Dot/Icm type IV secretion system (T4SS) delivers effector proteins into host cells during infection. Despite its significance as a potential drug target, our current understanding of its atomic structure is limited to isolated subcomplexes. In this study, we used subtomogram averaging and integrative modeling to construct a nearly-complete model of the Dot/Icm T4SS accounting for seventeen protein components. We locate and provide insights into the structure and function of six new components including DotI, DotJ, DotU, IcmF, IcmT, and IcmX. We find that the cytosolic N-terminal domain of IcmF, a key protein forming a central hollow cylinder, interacts with DotU, providing insight into previously uncharacterized density. Furthermore, our model, in combination with analyses of compositional heterogeneity, explains how the cytoplasmic ATPase DotO is connected to the periplasmic complex via interactions with membrane-bound DotI/DotJ proteins. Coupled with in situ infection data, our model offers new insights into the T4SS-mediated secretion mechanism. ; The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. Electron microscopy was performed in the Beckman Institute Resource Center for Transmission Electron Microscopy at Caltech and Pacific Northwest Center for Cryo-EM (PNCC). We thank the Liu lab for sharing data and expertise in using I3 to resolve the DotO hexamer of dimers. Y.L. was supported by a Jane Coffin Childs Memorial Fund for Medical Research post-doctoral fellowship. This work was supported by the National Institutes of Health (grant R01-AI127401 to G.J.J.). AUTHOR CONTRIBUTIONS. P.D. prepared samples, reconstructed tomograms and picked particles for a subset of data, performed subtomogram averaging, performed data exploration, located proteins forming the system, participated in building the model, drafted the manuscript, and prepared ... |
| نوع الوثيقة: |
report |
| اللغة: |
unknown |
| العلاقة: |
https://doi.org/10.1101/2023.03.22.533729Test; oai:authors.library.caltech.edu:47yv1-y5250; eprintid:120378; resolverid:CaltechAUTHORS:20230324-517798000.1 |
| DOI: |
10.1101/2023.03.22.533729 |
| الإتاحة: |
https://doi.org/10.1101/2023.03.22.533729Test |
| حقوق: |
info:eu-repo/semantics/openAccess ; Other |
| رقم الانضمام: |
edsbas.C888EB1F |
| قاعدة البيانات: |
BASE |
