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

• Published in: FEBS letters Vol. 587; no. 21; pp. 3412 - 3416
• Main Authors: Kaplan-Türköz, Burcu, Koelblen, Thomas, Felix, Christine, Candusso, Marie-Pierre, O’Callaghan, David, Vergunst, Annette C., Terradot, Laurent
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.11.2013; Wiley
• 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; X-ray crystallography; TLR; BtpA; Structural mimicry; Brucella; TIR domain
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.09.007

•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)