In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 17, No. 1 ( 2021-1-7), p. e1008169-
Abstract:
Streptococcus pyogenes (Group A streptococcus; GAS) is an important human pathogen responsible for mild to severe, life-threatening infections. GAS expresses a wide range of virulence factors, including the M family proteins. The M proteins allow the bacteria to evade parts of the human immune defenses by triggering the formation of a dense coat of plasma proteins surrounding the bacteria, including IgGs. However, the molecular level details of the M1-IgG interaction have remained unclear. Here, we characterized the structure and dynamics of this interaction interface in human plasma on the surface of live bacteria using integrative structural biology, combining cross-linking mass spectrometry and molecular dynamics (MD) simulations. We show that the primary interaction is formed between the S-domain of M1 and the conserved IgG Fc-domain. In addition, we show evidence for a so far uncharacterized interaction between the A-domain and the IgG Fc-domain. Both these interactions mimic the protein G-IgG interface of group C and G streptococcus. These findings underline a conserved scavenging mechanism used by GAS surface proteins that block the IgG-receptor (FcγR) to inhibit phagocytic killing. We additionally show that we can capture Fab-bound IgGs in a complex background and identify XLs between the constant region of the Fab-domain and certain regions of the M1 protein engaged in the Fab-mediated binding. Our results elucidate the M1-IgG interaction network involved in inhibition of phagocytosis and reveal important M1 peptides that can be further investigated as future vaccine targets.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1008169
DOI:
10.1371/journal.pcbi.1008169.g001
DOI:
10.1371/journal.pcbi.1008169.g002
DOI:
10.1371/journal.pcbi.1008169.g003
DOI:
10.1371/journal.pcbi.1008169.g004
DOI:
10.1371/journal.pcbi.1008169.g005
DOI:
10.1371/journal.pcbi.1008169.t001
DOI:
10.1371/journal.pcbi.1008169.s001
DOI:
10.1371/journal.pcbi.1008169.s002
DOI:
10.1371/journal.pcbi.1008169.s003
DOI:
10.1371/journal.pcbi.1008169.s004
DOI:
10.1371/journal.pcbi.1008169.s005
DOI:
10.1371/journal.pcbi.1008169.s006
DOI:
10.1371/journal.pcbi.1008169.s007
DOI:
10.1371/journal.pcbi.1008169.s008
DOI:
10.1371/journal.pcbi.1008169.s009
DOI:
10.1371/journal.pcbi.1008169.s010
DOI:
10.1371/journal.pcbi.1008169.s011
DOI:
10.1371/journal.pcbi.1008169.s012
DOI:
10.1371/journal.pcbi.1008169.s013
DOI:
10.1371/journal.pcbi.1008169.s014
DOI:
10.1371/journal.pcbi.1008169.s015
DOI:
10.1371/journal.pcbi.1008169.s016
DOI:
10.1371/journal.pcbi.1008169.s017
DOI:
10.1371/journal.pcbi.1008169.s018
DOI:
10.1371/journal.pcbi.1008169.s019
DOI:
10.1371/journal.pcbi.1008169.s020
DOI:
10.1371/journal.pcbi.1008169.s021
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2193340-6
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