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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
MyD88 self-assembles into supramolecular filaments to amplify NF-κB signaling
Jia Wang1, Xincheng Zhong1, Chenyi Liao2
1State Key Laboratory of Membrane Biology, School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.
Fundamental Research
|August 1, 2026
Summary
Myeloid differentiation primary response 88 (MyD88) self-assembles into filaments for innate immune signaling. Mutations disrupt these structures, potentially driving disease development.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- Myeloid differentiation primary response 88 (MyD88) is crucial for innate immunity.
- The precise molecular mechanisms underlying MyD88 mutation-related diseases are not fully understood.
Purpose of the Study:
- To elucidate the self-assembly mechanism of MyD88 as a signal amplification machinery.
- To investigate the structural and functional impact of specific MyD88 mutations.
Main Methods:
- Filament formation assays using MyD88 domains.
- Analysis of loss-of-function (L93P) and gain-of-function (L252P) mutants.
- Atomic molecular dynamics simulations.
Main Results:
- The death domain (MyD88DD) and intermediate domain (MyD88ID) form the minimal filament unit, modulated by the TIR domain (MyD88TIR).
- The L93P mutation disrupts MyD88 filaments by altering MyD88DD conformation.
- The L252P mutation converts filaments into speckles by inducing α-helix unfolding and BB-loop exposure.
Conclusions:
- MyD88 self-assembly into higher-order structures is essential for its function.
- Pathological mutations alter MyD88 assembly, impacting its structure and function.
- These alterations may contribute to the pathogenesis of various diseases.
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