biostudies-literatureUnknown110(17)Snyder GAIntramural NIH HHSThe Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demonProceedings of the National Academy of Sciences of the United States of America6985-90https://www.ebi.ac.uk/biostudies/studies/S-EPMC3637702biostudies-literatureMolecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.PMC3637702Jiang JFresquez TChen KWaldhuber ATjandra NDurr SSnyder GAMiethke TSmith PCirl CRommler FSnyder NXiao TSfalseMolecular mechanisms for the subversion of MyD88 signaling by TcpC from virulent uropathogenic Escherichia coli.The Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demon2013-01-01T00:00:00Z2013 Apr2026-04-13T13:50:47.395Z2019-03-26T22:32:19ZS-EPMC36377022356923010.1073/pnas.1215770110