2Z5V

Solution structure of the TIR domain of human MyD88


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling.

Ohnishi, H.Tochio, H.Kato, Z.Orii, K.E.Li, A.Kimura, T.Hiroaki, H.Kondo, N.Shirakawa, M.

(2009) Proc Natl Acad Sci U S A 

  • DOI: https://doi.org/10.1073/pnas.0812956106
  • Primary Citation of Related Structures:  
    2Z5V

  • 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.


  • Organizational Affiliation

    Department of Pediatrics, Graduate School of Medicine, Center for Emerging Infectious Diseases, and Center for Advanced Drug Research, Gifu University, Gifu, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Myeloid differentiation primary response protein MyD88149Homo sapiensMutation(s): 0 
Gene Names: MYD88
UniProt & NIH Common Fund Data Resources
Find proteins for Q99836 (Homo sapiens)
Explore Q99836 
Go to UniProtKB:  Q99836
PHAROS:  Q99836
GTEx:  ENSG00000172936 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99836
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-05
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2022-03-16
    Changes: Database references, Derived calculations
  • Version 1.3: 2024-05-29
    Changes: Data collection