Structure of the Toll/interleukin 1 receptor (TIR) domain of the immunosuppressive Brucella effector BtpA/Btp1/TcpB

•Crystal structure of BtpA TIR domain.•BtpA forms a TIR:TIR dimer secured by a N-terminal α-tail.•The structure suggests different modes of action for BtpA compared to other bacterial TIR proteins. BtpA/Btp1/TcpB is a virulence factor produced by Brucella species that possesses a Toll interleukin-1...

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Bibliographic Details
Published in:FEBS letters 2013-11, Vol.587 (21), p.3412-3416
Main Authors: Kaplan-Türköz, Burcu, Koelblen, Thomas, Felix, Christine, Candusso, Marie-Pierre, O’Callaghan, David, Vergunst, Annette C., Terradot, Laurent
Format: Article
Language:English
Subjects:
Bacterial Proteins
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Brucella
Brucella melitensis
Brucella melitensis - immunology
Brucella melitensis - metabolism
BtpA
Humans
Life Sciences
Models, Molecular
Paracoccus denitrificans
Paracoccus denitrificans - metabolism
Protein Multimerization
Protein Structure, Tertiary
Receptors, Interleukin-1
Receptors, Interleukin-1 - chemistry
Receptors, Interleukin-1 - metabolism
Structural mimicry
Structure-Activity Relationship
TIR domain
TLR
Virulence Factors
Virulence Factors - chemistry
Virulence Factors - metabolism
X-ray crystallography
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Summary:•Crystal structure of BtpA TIR domain.•BtpA forms a TIR:TIR dimer secured by a N-terminal α-tail.•The structure suggests different modes of action for BtpA compared to other bacterial TIR proteins. BtpA/Btp1/TcpB is a virulence factor produced by Brucella species that possesses a Toll interleukin-1 receptor (TIR) domain. Once delivered into the host cell, BtpA interacts with MyD88 to interfere with TLR signalling and modulates microtubule dynamics. Here the crystal structure of the BtpA TIR domain at 3.15Å is presented. The structure shows a dimeric arrangement of a canonical TIR domain, similar to the Paracoccus denitrificans Tir protein but secured by a unique long N-terminal α-tail that packs against the TIR:TIR dimer. Structure-based mutations and multi-angle light scattering experiments characterized the BtpA dimer conformation in solution. The structure of BtpA will help with studies to understand the mechanisms involved in its interactions with MyD88 and with microtubules. BtpA and BtpAbind by x-ray crystallography (View interaction)
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2013.09.007