Structure of the Toll/interleukin 1 receptor (TIR) domain of the immunosuppressive Brucella effector BtpA/Btp1/TcpB.
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 3.15 Å 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.
UMR 5086, BMSSI, CNRS - Université Lyon 1, Institut de Biologie et Chimie des Protéines, 7 passage du Vercors, F-69367, France.
Burcu
B
Kaplan-Türköz
Thomas
T
Koelblen
Christine
C
Felix
Marie-Pierre
MP
Candusso
David
D
O'Callaghan
Annette C
AC
Vergunst
Laurent
L
Terradot
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D017347:Brucella melitensis / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010231:Paracoccus denitrificans / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D037521:Virulence Factors / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D017472:Receptors, Interleukin-1; D037521:Virulence Factors
Brucella; BtpA; Structural mimicry; TIR domain; TLR; X-ray crystallography