Dynamic interaction of the Yersinia pseudotuberculosis type three secretion system proteins LcrV and LcrG
(2025) In Protein Science 35(1).- Abstract
Yersinia pathogenicity is dependent on polarized translocation of effector proteins via the type III secretion system (T3SS). The tip complex situated on the needle structure of the T3SS is required for contact with the eukaryotic host membrane and is to an extent composed of pentameric LcrV. LcrV is a multifunctional protein that also acts as a regulator of the T3SS by virtue of forming a high-affinity complex in the cytoplasm with its chaperone, LcrG. By employing a structure-based approach centered on mass spectrometry, FRET and NMR spectroscopy, we demonstrated that the LcrV-LcrG complex is best described as a multivalent complex, and that the N-terminal domain of LcrV contributes by negatively affecting the LcrG binding affinity.... (More)
Yersinia pathogenicity is dependent on polarized translocation of effector proteins via the type III secretion system (T3SS). The tip complex situated on the needle structure of the T3SS is required for contact with the eukaryotic host membrane and is to an extent composed of pentameric LcrV. LcrV is a multifunctional protein that also acts as a regulator of the T3SS by virtue of forming a high-affinity complex in the cytoplasm with its chaperone, LcrG. By employing a structure-based approach centered on mass spectrometry, FRET and NMR spectroscopy, we demonstrated that the LcrV-LcrG complex is best described as a multivalent complex, and that the N-terminal domain of LcrV contributes by negatively affecting the LcrG binding affinity. The N-terminal domain of LcrV is dynamic and undergoes a conformational change to accommodate LcrG binding. 19F NMR spectroscopy analysis suggests that the conformational change is an intrinsic property of the protein, which agrees with a conformational selection model. An analysis of effector secretion into a culture supernatant demonstrated that the low synthesis and low secretion phenotypes of a LcrV mutant where the N-terminal domain has been removed are linked to the structure, interactions and stability of the LcrV N-terminal domain. In summary, our results add insights into the dynamics of LcrV and its complex with LcrG.
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- author
- Mangu, Jagadish Chandra Kumar ; Rogne, Per ; Mattsson, Jonna LU ; Hultgren, Lucas LU ; Gahlot, Kumar D. ; Lamy, Anaïs ; Berntsson, Ronnie P.A. ; Johansson, Lennart B.Å. LU ; Francis, Matthew S. and Wolf-Watz, Magnus
- organization
- publishing date
- 2025-12-22
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- chaperone LcrG, needle tip complex, pentameric LcrV, protein conformational switch, type III secretion system, Yersinia pathogenicity
- in
- Protein Science
- volume
- 35
- issue
- 1
- article number
- e70400
- publisher
- The Protein Society
- external identifiers
-
- pmid:41427733
- scopus:105025378778
- ISSN
- 0961-8368
- DOI
- 10.1002/pro.70400
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
- id
- 66514c1a-31ba-4d6a-8e98-1203e2263fbb
- date added to LUP
- 2026-03-24 15:49:18
- date last changed
- 2026-07-30 09:18:49
@article{66514c1a-31ba-4d6a-8e98-1203e2263fbb,
abstract = {{<p>Yersinia pathogenicity is dependent on polarized translocation of effector proteins via the type III secretion system (T3SS). The tip complex situated on the needle structure of the T3SS is required for contact with the eukaryotic host membrane and is to an extent composed of pentameric LcrV. LcrV is a multifunctional protein that also acts as a regulator of the T3SS by virtue of forming a high-affinity complex in the cytoplasm with its chaperone, LcrG. By employing a structure-based approach centered on mass spectrometry, FRET and NMR spectroscopy, we demonstrated that the LcrV-LcrG complex is best described as a multivalent complex, and that the N-terminal domain of LcrV contributes by negatively affecting the LcrG binding affinity. The N-terminal domain of LcrV is dynamic and undergoes a conformational change to accommodate LcrG binding. <sup>19</sup>F NMR spectroscopy analysis suggests that the conformational change is an intrinsic property of the protein, which agrees with a conformational selection model. An analysis of effector secretion into a culture supernatant demonstrated that the low synthesis and low secretion phenotypes of a LcrV mutant where the N-terminal domain has been removed are linked to the structure, interactions and stability of the LcrV N-terminal domain. In summary, our results add insights into the dynamics of LcrV and its complex with LcrG.</p>}},
author = {{Mangu, Jagadish Chandra Kumar and Rogne, Per and Mattsson, Jonna and Hultgren, Lucas and Gahlot, Kumar D. and Lamy, Anaïs and Berntsson, Ronnie P.A. and Johansson, Lennart B.Å. and Francis, Matthew S. and Wolf-Watz, Magnus}},
issn = {{0961-8368}},
keywords = {{chaperone LcrG; needle tip complex; pentameric LcrV; protein conformational switch; type III secretion system; Yersinia pathogenicity}},
language = {{eng}},
month = {{12}},
number = {{1}},
publisher = {{The Protein Society}},
series = {{Protein Science}},
title = {{Dynamic interaction of the Yersinia pseudotuberculosis type three secretion system proteins LcrV and LcrG}},
url = {{http://dx.doi.org/10.1002/pro.70400}},
doi = {{10.1002/pro.70400}},
volume = {{35}},
year = {{2025}},
}