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Long charge-rich alpha-helices in systemic autoantigens
J G Dohlman1, A Lupas, M Carson
1Connective Tissue Diseases Section, NIAMS, National Institutes of Health, Bethesda, Md. 20892.
Biochemical and Biophysical Research Communications
|September 15, 1993
Summary
Computer analysis revealed that coiled-coil alpha-helices are common in human autoantigens, suggesting they contribute to autoimmune disease development. These structures may explain why certain proteins trigger immune responses in autoimmune diseases.
Area of Science:
- Immunology
- Structural Biology
- Computational Biology
Background:
- Autoimmune diseases involve immune responses against self-proteins (autoantigens).
- The high immunogenicity of autoantigens compared to non-autoantigens is not fully understood.
- Specific protein structures may contribute to autoantigenicity.
Purpose of the Study:
- To identify distinctive sequence patterns in human autoantigens using computational methods.
- To investigate the potential role of coiled-coil alpha-helices in autoantigenicity.
Main Methods:
- Bioinformatic analysis of sequenced human autoantigens.
- Prediction of coiled-coil alpha-helix formation using computational algorithms.
- Comparison of autoantigen sequences with general human protein databases (Swissprot, Brookhaven).
Main Results:
- Coiled-coil alpha-helices (longer than 27 residues, probability >0.9) were found in 36.7% of analyzed human autoantigens.
- This prevalence is significantly higher than in general human protein databases (8.7% in Swissprot, 1.1% in Brookhaven).
- These coiled-coils are longer, more charged, and possess heptad repeat multivalency compared to typical globular protein helices.
Conclusions:
- Coiled-coil alpha-helical structures are prevalent in human autoantigens, including those associated with systemic autoimmune diseases.
- These structures correlate with known autoantibody epitopes and likely contribute to the immunogenic potential of autoantigens.
- Systemic autoantigens often feature basic properties or extended, charged segments like coiled-coils.