2M1X

TICAM-1 TIR domain structure

Summary for 2M1X

• Entry DOI: 10.2210/pdb2m1x/pdb
• Related: 2M1W
• NMR Information: BMRB: 18883
• Descriptor: TIR domain-containing adapter molecule 1 (1 entity in total)
• Functional Keywords: tir domain, ticam-1, interferon, trif, innate immunity, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 19132.69

Authors

Enokizono, Y.,Kumeta, H.,Funami, K.,Horiuchi, M.,Sarmiento, J.,Yamashita, K.,Standley, D.M.,Matsumoto, M.,Seya, T.,Inagaki, F. (deposition date: 2012-12-07, release date: 2014-01-15, Last modification date: 2024-05-15)

Primary citation

Enokizono, Y.,Kumeta, H.,Funami, K.,Horiuchi, M.,Sarmiento, J.,Yamashita, K.,Standley, D.M.,Matsumoto, M.,Seya, T.,Inagaki, F.
Structures and interface mapping of the TIR domain-containing adaptor molecules involved in interferon signaling.
Proc.Natl.Acad.Sci.USA, 110:19908-19913, 2013

PubMed Abstract: Homotypic and heterotypic interactions between Toll/interleukin-1 receptor (TIR) domains in Toll-like receptors (TLRs) and downstream adaptors are essential to evoke innate immune responses. However, such oligomerization properties present intrinsic difficulties in structural studies of TIR domains. Here, using BB-loop mutations that disrupt homotypic interactions, we determined the structures of the monomeric TIR domain-containing adaptor molecule (TICAM)-1 and TICAM-2 TIR domains. Docking of the monomeric structures, together with yeast two hybrid-based mutagenesis assays, reveals that the homotypic interaction between TICAM-2 TIR is indispensable to present a scaffold for recruiting the monomeric moiety of the TICAM-1 TIR dimer. This result proposes a unique idea that oligomerization of upstream TIR domains is crucial for binding of downstream TIR domains. Furthermore, the bivalent nature of each TIR domain dimer can generate a large signaling complex under the activated TLRs, which would recruit downstream signaling molecules efficiently. This model is consistent with previous reports that BB-loop mutants completely abrogate downstream signaling.

PubMed: 24255114
DOI: 10.1073/pnas.1222811110

Experimental method

SOLUTION NMR