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Structural model of a Porphyromonas gingivalis type IX secretion system shuttle complex

DOI: 10.1016/j.jmb.2022.167871 DOI Help

Authors: Ben Dorgan (King’s College London; Queen Mary University of London) , Yichao Liu (King’s College London) , Sunjun Wang (King's College London) , Joseph Aduse-Opoku (King’s College London) , Sara B. M. Whittaker (University of Birmingham) , Mark A. J. Roberts (Queen Mary University of London) , Christian D. Lorenz (King’s College London) , Mike A. Curtis (King’s College London) , James A. Garnett (King’s College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Molecular Biology , VOL 7

State: Published (Approved)
Published: October 2022
Diamond Proposal Number(s): 26325

Open Access Open Access

Abstract: Porphyromonas gingivalis is a gram-negative oral anaerobic pathogen and is one of the key causative agents of periodontitis. P. gingivalis utilises a range of virulence factors, including the cysteine protease RgpB, to drive pathogenesis and these are exported and attached to the cell surface via the type IX secretion system (T9SS). All cargo proteins possess a conserved C-terminal signal domain (CTD) which is recognised by the T9SS, and the outer membrane β-barrel protein PorV (PG0027/LptO) can interact with cargo proteins as they are exported to the bacterial surface. Using a combination of solution nuclear magnetic resonance (NMR) spectroscopy, biochemical analyses, machine-learning-based modelling and molecular dynamics (MD) simulations, we present a structural model of a PorV:RgpB-CTD complex from P. gingivalis. This is the first structural insight into CTD recognition by the T9SS and shows how the conserved motifs in the CTD are the primary sites that mediate binding. In PorV, interactions with extracellular surface loops are important for binding the CTD, and together these appear to cradle and lock RgpB-CTD in place. This work provides insight into cargo recognition by PorV but may also have important implications for understanding other aspects of type-IX dependent secretion.

Journal Keywords: Porphyromonas gingivalis; T9SS; CTD; RgpB; PorV

Diamond Keywords: Bacteria; Gum Disease

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS

Added On: 02/11/2022 08:31

Documents:
1-s2.0-S0022283622004910-main.pdf

Discipline Tags:

Pathogens Infectious Diseases Dentistry Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)