Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Infektionsbiologie     Collection: Department of Cellular Microbiology     Display Documents



  history
ID: 572512.0, MPI für Infektionsbiologie / Department of Cellular Microbiology
Crystal Structure of PrgI-SipD: Insight into a Secretion Competent State of the Type Three Secretion System Needle Tip and its Interaction with Host Ligands
Authors:Lunelli, Michele; Hurwitz, Robert; Lambers, Jutta; Kolbe, Michael
Language:English
Date of Publication (YYYY-MM-DD):2011-08
Title of Journal:PLoS Pathogens
Journal Abbrev.:PLoS Pathog.
Volume:7
Issue / Number:8
Sequence Number of Article:e1002163
Copyright:Lunelli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Many infectious Gram-negative bacteria, including Salmonella typhimurium, require a Type Three Secretion System (T3SS) to translocate virulence factors into host cells. The T3SS consists of a membrane protein complex and an extracellular needle together that form a continuous channel. Regulated secretion of virulence factors requires the presence of SipD at the T3SS needle tip in S. typhimurium. Here we report three-dimensional structures of individual SipD, SipD in fusion with the needle subunit PrgI, and of SipD: PrgI in complex with the bile salt, deoxycholate. Assembly of the complex involves major conformational changes in both SipD and PrgI. This rearrangement is mediated via a p bulge in the central SipD helix and is stabilized by conserved amino acids that may allow for specificity in the assembly and composition of the tip proteins. Five copies each of the needle subunit PrgI and SipD form the T3SS needle tip complex. Using surface plasmon resonance spectroscopy and crystal structure analysis we found that the T3SS needle tip complex binds deoxycholate with micromolar affinity via a cleft formed at the SipD: PrgI interface. In the structure-based three-dimensional model of the T3SS needle tip, the bound deoxycholate faces the host membrane. Recently, binding of SipD with bile salts present in the gut was shown to impede bacterial infection. Binding of bile salts to the SipD: PrgI interface in this particular arrangement may thus inhibit the T3SS function. The structures presented in this study provide insight into the open state of the T3SS needle tip. Our findings present the atomic details of the T3SS arrangement occurring at the pathogen-host interface.
External Publication Status:published
Document Type:Article
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Cellular Microbiology
MPI für Infektionsbiologie/Core Facilities
Identifiers:ISI:000294298100009 [ID No:1]
ISSN:1553-7366 [ID No:2]
DOI:10.1371/journal.ppat.1002163 [ID No:3]
Full Text:
You have privileges to view the following file(s):
PLoS_Pathogens_2011_7_e1002163.pdf  [656,00 Kb]   
 
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.