Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.

A pre-requisite for bacterial pathogenesis is the successful interaction of a pathogen with a host. One mechanism used by a broad range of Gram negative bacterial pathogens is to deliver effector proteins directly into host cells through a dedicated type III secretion system where they modulate host...

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Main Authors: Allister Crow, Paul R Race, Grégory Jubelin, Carolina Varela Chavez, Jean-Michel Escoubas, Eric Oswald, Mark J Banfield
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005582&type=printable
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author Allister Crow
Paul R Race
Grégory Jubelin
Carolina Varela Chavez
Jean-Michel Escoubas
Eric Oswald
Mark J Banfield
author_facet Allister Crow
Paul R Race
Grégory Jubelin
Carolina Varela Chavez
Jean-Michel Escoubas
Eric Oswald
Mark J Banfield
author_sort Allister Crow
collection DOAJ
description A pre-requisite for bacterial pathogenesis is the successful interaction of a pathogen with a host. One mechanism used by a broad range of Gram negative bacterial pathogens is to deliver effector proteins directly into host cells through a dedicated type III secretion system where they modulate host cell function. The cycle inhibiting factor (Cif) family of effector proteins, identified in a growing number of pathogens that harbour functional type III secretion systems and have a wide host range, arrest the eukaryotic cell cycle. Here, the crystal structures of Cifs from the insect pathogen/nematode symbiont Photorhabdus luminescens (a gamma-proteobacterium) and human pathogen Burkholderia pseudomallei (a beta-proteobacterium) are presented. Both of these proteins adopt an overall fold similar to the papain sub-family of cysteine proteases, as originally identified in the structure of a truncated form of Cif from Enteropathogenic E. coli (EPEC), despite sharing only limited sequence identity. The structure of an N-terminal region, referred to here as the 'tail-domain' (absent in the EPEC Cif structure), suggests a surface likely to be involved in host-cell substrate recognition. The conformation of the Cys-His-Gln catalytic triad is retained, and the essential cysteine is exposed to solvent and addressable by small molecule reagents. These structures and biochemical work contribute to the rapidly expanding literature on Cifs, and direct further studies to better understand the molecular details of the activity of these proteins.
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spelling doaj-art-9eb2182beea542148ede3bfbef2b1d262025-08-20T02:00:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0145e558210.1371/journal.pone.0005582Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.Allister CrowPaul R RaceGrégory JubelinCarolina Varela ChavezJean-Michel EscoubasEric OswaldMark J BanfieldA pre-requisite for bacterial pathogenesis is the successful interaction of a pathogen with a host. One mechanism used by a broad range of Gram negative bacterial pathogens is to deliver effector proteins directly into host cells through a dedicated type III secretion system where they modulate host cell function. The cycle inhibiting factor (Cif) family of effector proteins, identified in a growing number of pathogens that harbour functional type III secretion systems and have a wide host range, arrest the eukaryotic cell cycle. Here, the crystal structures of Cifs from the insect pathogen/nematode symbiont Photorhabdus luminescens (a gamma-proteobacterium) and human pathogen Burkholderia pseudomallei (a beta-proteobacterium) are presented. Both of these proteins adopt an overall fold similar to the papain sub-family of cysteine proteases, as originally identified in the structure of a truncated form of Cif from Enteropathogenic E. coli (EPEC), despite sharing only limited sequence identity. The structure of an N-terminal region, referred to here as the 'tail-domain' (absent in the EPEC Cif structure), suggests a surface likely to be involved in host-cell substrate recognition. The conformation of the Cys-His-Gln catalytic triad is retained, and the essential cysteine is exposed to solvent and addressable by small molecule reagents. These structures and biochemical work contribute to the rapidly expanding literature on Cifs, and direct further studies to better understand the molecular details of the activity of these proteins.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005582&type=printable
spellingShingle Allister Crow
Paul R Race
Grégory Jubelin
Carolina Varela Chavez
Jean-Michel Escoubas
Eric Oswald
Mark J Banfield
Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.
PLoS ONE
title Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.
title_full Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.
title_fullStr Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.
title_full_unstemmed Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.
title_short Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.
title_sort crystal structures of cif from bacterial pathogens photorhabdus luminescens and burkholderia pseudomallei
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005582&type=printable
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