Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain

Summary: Infections typically begin with pathogens adhering to host cells. For bacteria, this adhesion can occur through specific ligand-binding domains. We identify a 20-kDa peptide-binding domain (PBD) in a 1.5-MDa RTX adhesin of a Gram-negative marine bacterium that colonizes diatoms. The crystal...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shuaiqi Guo, Hossein Zahiri, Corey Stevens, Daniel C. Spaanderman, Lech-Gustav Milroy, Christian Ottmann, Luc Brunsveld, Ilja K. Voets, Peter L. Davies
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	structural biology bacteria-host interaction bacterial adhesins X-ray crystallography peptide inhibitors peptide-binding domain Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6c8e93c1682b4badaad38e01db08d15d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6c8e93c1682b4badaad38e01db08d15d
record_format	dspace
spelling	oai:doaj.org-article:6c8e93c1682b4badaad38e01db08d15d2021-11-18T04:47:51ZMolecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain2211-124710.1016/j.celrep.2021.110002https://doaj.org/article/6c8e93c1682b4badaad38e01db08d15d2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014807https://doaj.org/toc/2211-1247Summary: Infections typically begin with pathogens adhering to host cells. For bacteria, this adhesion can occur through specific ligand-binding domains. We identify a 20-kDa peptide-binding domain (PBD) in a 1.5-MDa RTX adhesin of a Gram-negative marine bacterium that colonizes diatoms. The crystal structure of this Ca2+-dependent PBD suggests that it may bind the C termini of host cell-surface proteins. A systematic peptide library analysis reveals an optimal tripeptide sequence with 30-nM affinity for the PBD, and X-ray crystallography details its peptide-protein interactions. Binding of the PBD to the diatom partner of the bacteria can be inhibited or competed away by the peptide, providing a molecular basis for inhibiting bacterium-host interactions. We further show that this PBD is found in other bacteria, including human pathogens such as Vibrio cholerae and Aeromonas veronii. Here, we produce the PBD ortholog from A. veronii and demonstrate, using the same peptide inhibitor, how pathogens may be prevented from adhering to their hosts.Shuaiqi GuoHossein ZahiriCorey StevensDaniel C. SpaandermanLech-Gustav MilroyChristian OttmannLuc BrunsveldIlja K. VoetsPeter L. DaviesElsevierarticlestructural biologybacteria-host interactionbacterial adhesinsX-ray crystallographypeptide inhibitorspeptide-binding domainBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 7, Pp 110002- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	structural biology bacteria-host interaction bacterial adhesins X-ray crystallography peptide inhibitors peptide-binding domain Biology (General) QH301-705.5
spellingShingle	structural biology bacteria-host interaction bacterial adhesins X-ray crystallography peptide inhibitors peptide-binding domain Biology (General) QH301-705.5 Shuaiqi Guo Hossein Zahiri Corey Stevens Daniel C. Spaanderman Lech-Gustav Milroy Christian Ottmann Luc Brunsveld Ilja K. Voets Peter L. Davies Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain
description	Summary: Infections typically begin with pathogens adhering to host cells. For bacteria, this adhesion can occur through specific ligand-binding domains. We identify a 20-kDa peptide-binding domain (PBD) in a 1.5-MDa RTX adhesin of a Gram-negative marine bacterium that colonizes diatoms. The crystal structure of this Ca2+-dependent PBD suggests that it may bind the C termini of host cell-surface proteins. A systematic peptide library analysis reveals an optimal tripeptide sequence with 30-nM affinity for the PBD, and X-ray crystallography details its peptide-protein interactions. Binding of the PBD to the diatom partner of the bacteria can be inhibited or competed away by the peptide, providing a molecular basis for inhibiting bacterium-host interactions. We further show that this PBD is found in other bacteria, including human pathogens such as Vibrio cholerae and Aeromonas veronii. Here, we produce the PBD ortholog from A. veronii and demonstrate, using the same peptide inhibitor, how pathogens may be prevented from adhering to their hosts.
format	article
author	Shuaiqi Guo Hossein Zahiri Corey Stevens Daniel C. Spaanderman Lech-Gustav Milroy Christian Ottmann Luc Brunsveld Ilja K. Voets Peter L. Davies
author_facet	Shuaiqi Guo Hossein Zahiri Corey Stevens Daniel C. Spaanderman Lech-Gustav Milroy Christian Ottmann Luc Brunsveld Ilja K. Voets Peter L. Davies
author_sort	Shuaiqi Guo
title	Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain
title_short	Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain
title_full	Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain
title_fullStr	Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain
title_full_unstemmed	Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain
title_sort	molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6c8e93c1682b4badaad38e01db08d15d
work_keys_str_mv	AT shuaiqiguo molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT hosseinzahiri molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT coreystevens molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT danielcspaanderman molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT lechgustavmilroy molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT christianottmann molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT lucbrunsveld molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT iljakvoets molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain AT peterldavies molecularbasisforinhibitionofadhesinmediatedbacterialhostinteractionsthroughapeptidebindingdomain
_version_	1718425044924760064

Molecular basis for inhibition of adhesin-mediated bacterial-host interactions through a peptide-binding domain

Ejemplares similares