Side-chain specificities and molecular modelling of peptide determinants for two anti-Sm B/B' autoantibodies.
Autoantibodies binding the Sm B and B' peptides (B/B') are commonly associated with systemic lupus erythematosus in man and in MRL lpr/lpr mice. The linear antigenic regions of two anti-Sm B/B' murine monoclonal auto-antibodies have been mapped using overlapping octapeptides. Unique epitopes are identified by each antibody. Monoclonal KSm-5 recognizes the peptide, PPPGMRPP, which is repeated three times in the Sm B polypeptide. KSm 3 preferably binds to two similar, almost neighboring octapeptides, PPPGIRGP and PGIRGPPP. The two monoclonal antibodies do not cross react. These regions of Sm B/B' are major areas of antigenicity in human sera. Amino acid deletion and substitution in antigenic octapeptides show that binding to the KSm-5 epitope is lost with most modifications. Molecular dynamic modelling suggests that when PPPGMRPP is substituted in the sixth position arginine, KSm/5 binding may be associated with a shared peptide backbone structure rather than charge or hydrophobicity of the substituted amino acid. In contrast, binding of KSm-3 to PPPGIRGP is abolished when the sixth position arginine is substituted by any other amino acid. Substitution at arginine and modelling experiments, therefore, suggest very different mech-anisms of binding. Autoantibodies may bind quite different features of similar peptide structures.
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- snRNP Core Proteins
- Ribonucleoproteins, Small Nuclear
- Protein Conformation
- Oligopeptides
- Molecular Sequence Data
- Models, Molecular
- Mice
- Immunology
- Epitopes
- Computer Simulation
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- snRNP Core Proteins
- Ribonucleoproteins, Small Nuclear
- Protein Conformation
- Oligopeptides
- Molecular Sequence Data
- Models, Molecular
- Mice
- Immunology
- Epitopes
- Computer Simulation