Structural and functional examination of Neisseria gonorrhoeae TfpC reveals a dynamic two-domain architecture required for type IV pilus function
- 1King's College London
Abstract
The Neisseria gonorrhoeae (Gc) Type IV pilus (T4p) is a critical apparatus for colonization and virulence. This molecular machine resides at the host-pathogen interface and mediates adherence to host cells, twitching motility, natural transformation, and resistance to oxidative agents. Previously, we identified a DUF4124 family, T4p component, TfpC. TfpC is required for full T4p elaboration, and deleting the tfpC gene reduced natural transformation competence and resulted in an under-piliated colony morphology. Our earlier models suggested TfpC is composed of an N-terminal transmembrane helix and a proline-rich disordered region followed by a C-terminal coiled-coil. Here, we used targeted structural and genetic approaches to define TfpC's molecular structure. Our new data show that TfpC's N-terminal domain forms a novel, dynamic three-stranded {beta}-sheet structure. These data indicate that the flexible disordered region acts as a linker between the N- and C-terminal domains. Functionally, we illustrate TfpC requires an acidic face within the C-terminal coiled-coil domain to mediate pilus biogenesis and function. This study characterizes a unique protein fold and family and defines the contributions of TfpC's domains to its function.
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BibTeX
@misc{nicholson2026structural,
title = {{Structural and functional examination of Neisseria gonorrhoeae TfpC reveals a dynamic two-domain architecture required for type IV pilus function}},
author = {K. R. Nicholson and M. Baczynska and E. Ploskon and P. Simpson and A. Oregioni and C. Lorenz and H. S. SEIFERT and J. Garnett},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.764878},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764878v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Structural and functional examination of Neisseria gonorrhoeae TfpC reveals a dynamic two-domain architecture required for type IV pilus function
AU - K. R. Nicholson
AU - M. Baczynska
AU - E. Ploskon
AU - P. Simpson
AU - A. Oregioni
AU - C. Lorenz
AU - H. S. SEIFERT
AU - J. Garnett
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.764878
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.764878v1
AB - The Neisseria gonorrhoeae (Gc) Type IV pilus (T4p) is a critical apparatus for colonization and virulence. This molecular machine resides at the host-pathogen interface and mediates adherence to host cells, twitching motility, natural transformation, and resistance to oxidative agents. Previously, we identified a DUF4124 family, T4p component, TfpC. TfpC is required for full T4p elaboration, and deleting the tfpC gene reduced natural transformation competence and resulted in an under-piliated colony morphology. Our earlier models suggested TfpC is composed of an N-terminal transmembrane helix and a proline-rich disordered region followed by a C-terminal coiled-coil. Here, we used targeted structural and genetic approaches to define TfpC's molecular structure. Our new data show that TfpC's N-terminal domain forms a novel, dynamic three-stranded {beta}-sheet structure. These data indicate that the flexible disordered region acts as a linker between the N- and C-terminal domains. Functionally, we illustrate TfpC requires an acidic face within the C-terminal coiled-coil domain to mediate pilus biogenesis and function. This study characterizes a unique protein fold and family and defines the contributions of TfpC's domains to its function.
ER -