2Z5V
Solution structure of the TIR domain of human MyD88
Summary for 2Z5V
| Entry DOI | 10.2210/pdb2z5v/pdb |
| NMR Information | BMRB: 11078 |
| Descriptor | Myeloid differentiation primary response protein MyD88 (1 entity in total) |
| Functional Keywords | signal transduction innate immunity, cytoplasm, immune response, inflammatory response, immune system |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: Q99836 |
| Total number of polymer chains | 1 |
| Total formula weight | 17387.32 |
| Authors | Ohnishi, H.,Tochio, H.,Hiroaki, H.,Kondo, N.,Kato, Z.,Shirakawa, M. (deposition date: 2007-07-19, release date: 2008-08-05, Last modification date: 2024-05-29) |
| Primary citation | Ohnishi, H.,Tochio, H.,Kato, Z.,Orii, K.E.,Li, A.,Kimura, T.,Hiroaki, H.,Kondo, N.,Shirakawa, M. Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling. Proc.Natl.Acad.Sci.USA, 2009 Cited by PubMed Abstract: Myeloid differentiating factor 88 (MyD88) and MyD88 adaptor-like (Mal) are adaptor molecules critically involved in the Toll-like receptor (TLR) 4 signaling pathway. While Mal has been proposed to serve as a membrane-sorting adaptor, MyD88 mediates signal transduction from activated TLR4 to downstream components. The Toll/Interleukin-1 receptor (TIR) domain of MyD88 is responsible for sorting and signaling via direct or indirect TIR-TIR interactions between Mal and TLR4. However, the molecular mechanisms involved in multiple interactions of the TIR domain remain unclear. The present study describes the solution structure of the MyD88 TIR domain. Reporter gene assays revealed that 3 discrete surface sites in the TIR domain of MyD88 are important for TLR4 signaling. Two of these sites were shown to mediate direct binding to the TIR domain of Mal. Interestingly, Mal-TIR, but not MyD88-TIR, directly binds to the cytosolic TIR domain of TLR4. These observations suggested that the heteromeric assembly of TIR domains of the receptor and adaptors constitutes the initial step of TLR4 intracellular signal transduction. PubMed: 19506249DOI: 10.1073/pnas.0812956106 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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