Long charge-rich alpha-helices in systemic autoantigens.
Autoimmune diseases are characterized by the presence of antibodies and T-cells targeting restricted sets of host proteins. This phenomenon may be due in part to greater non-specific immunogenicity for these proteins compared to others which are not autoantigenic. We used computer-based methods to analyze the sequenced human autoantigens for distinctive patterns of potential immunologic importance. Sequences longer than 27 residues predicted by these methods to form coiled-coil alpha-helices with a probability greater than 0.9 were detected in 40 of 109 (36.7%) of the known human autoantigens. These include many predominantly systemic disease-specific autoantigens not previously known to contain this structure. In comparison, 8.7% of human proteins in the Swissprot data base, and 1.1% of the proteins in the Brookhaven data base were found to contain such segments. These predicted coiled-coil alpha-helices are distinguished from most globular protein helices by greater length, higher charge content, and a heptad repeat multivalency. Coiled-coil segments correlate in part with known autoantibody epitopes and may contribute to autoantigenic potential. Systemic autoantigens generally are either basic or contain extended, multivalent, charge-rich segments such as coiled-coils.
Connective Tissue Diseases Section, NIAMS, National Institutes of Health, Bethesda, Md. 20892.
J G
JG
Dohlman
A
A
Lupas
M
M
Carson
D000465:Algorithms; D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry*; D001327:Autoimmune Diseases / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011336:Probability; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012984:Software
D001324:Autoantigens