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Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection

Streptococcus groups A and B cause serious infections, including early onset sepsis and meningitis in newborns. Rib domain-containing surface proteins are found associated with invasive strains and elicit protective immunity in animal models. Yet, despite their apparent importance in infection, the...

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Autores principales: Whelan, Fiona, Lafita, Aleix, Griffiths, Samuel C., Cooper, Rachael E. M., Whittingham, Jean L., Turkenburg, Johan P., Manfield, Iain W., St. John, Alexander N., Paci, Emanuele, Bateman, Alex, Potts, Jennifer R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936399/
https://www.ncbi.nlm.nih.gov/pubmed/31818940
http://dx.doi.org/10.1073/pnas.1911776116
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author Whelan, Fiona
Lafita, Aleix
Griffiths, Samuel C.
Cooper, Rachael E. M.
Whittingham, Jean L.
Turkenburg, Johan P.
Manfield, Iain W.
St. John, Alexander N.
Paci, Emanuele
Bateman, Alex
Potts, Jennifer R.
author_facet Whelan, Fiona
Lafita, Aleix
Griffiths, Samuel C.
Cooper, Rachael E. M.
Whittingham, Jean L.
Turkenburg, Johan P.
Manfield, Iain W.
St. John, Alexander N.
Paci, Emanuele
Bateman, Alex
Potts, Jennifer R.
author_sort Whelan, Fiona
collection PubMed
description Streptococcus groups A and B cause serious infections, including early onset sepsis and meningitis in newborns. Rib domain-containing surface proteins are found associated with invasive strains and elicit protective immunity in animal models. Yet, despite their apparent importance in infection, the structure of the Rib domain was previously unknown. Structures of single Rib domains of differing length reveal a rare case of domain atrophy through deletion of 2 core antiparallel strands, resulting in the loss of an entire sheet of the β-sandwich from an immunoglobulin-like fold. Previously, observed variation in the number of Rib domains within these bacterial cell wall-attached proteins has been suggested as a mechanism of immune evasion. Here, the structure of tandem domains, combined with molecular dynamics simulations and small angle X-ray scattering, suggests that variability in Rib domain number would result in differential projection of an N-terminal host-colonization domain from the bacterial surface. The identification of 2 further structures where the typical B-D-E immunoglobulin β-sheet is replaced with an α-helix further confirms the extensive structural malleability of the Rib domain.
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spelling pubmed-69363992019-12-31 Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection Whelan, Fiona Lafita, Aleix Griffiths, Samuel C. Cooper, Rachael E. M. Whittingham, Jean L. Turkenburg, Johan P. Manfield, Iain W. St. John, Alexander N. Paci, Emanuele Bateman, Alex Potts, Jennifer R. Proc Natl Acad Sci U S A Biological Sciences Streptococcus groups A and B cause serious infections, including early onset sepsis and meningitis in newborns. Rib domain-containing surface proteins are found associated with invasive strains and elicit protective immunity in animal models. Yet, despite their apparent importance in infection, the structure of the Rib domain was previously unknown. Structures of single Rib domains of differing length reveal a rare case of domain atrophy through deletion of 2 core antiparallel strands, resulting in the loss of an entire sheet of the β-sandwich from an immunoglobulin-like fold. Previously, observed variation in the number of Rib domains within these bacterial cell wall-attached proteins has been suggested as a mechanism of immune evasion. Here, the structure of tandem domains, combined with molecular dynamics simulations and small angle X-ray scattering, suggests that variability in Rib domain number would result in differential projection of an N-terminal host-colonization domain from the bacterial surface. The identification of 2 further structures where the typical B-D-E immunoglobulin β-sheet is replaced with an α-helix further confirms the extensive structural malleability of the Rib domain. National Academy of Sciences 2019-12-26 2019-12-09 /pmc/articles/PMC6936399/ /pubmed/31818940 http://dx.doi.org/10.1073/pnas.1911776116 Text en Copyright © 2019 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Whelan, Fiona
Lafita, Aleix
Griffiths, Samuel C.
Cooper, Rachael E. M.
Whittingham, Jean L.
Turkenburg, Johan P.
Manfield, Iain W.
St. John, Alexander N.
Paci, Emanuele
Bateman, Alex
Potts, Jennifer R.
Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection
title Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection
title_full Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection
title_fullStr Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection
title_full_unstemmed Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection
title_short Defining the remarkable structural malleability of a bacterial surface protein Rib domain implicated in infection
title_sort defining the remarkable structural malleability of a bacterial surface protein rib domain implicated in infection
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936399/
https://www.ncbi.nlm.nih.gov/pubmed/31818940
http://dx.doi.org/10.1073/pnas.1911776116
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