The goal of the proposed research is to understand the structural interactions which are important in the recognition of peptide and protein antigens by the immune system. In particular, the proposal is to determine the three-dimensional structures by x-ray crystallography of an anti-peptide Fab, an Fab-peptide complex and an Fab-protein complex to understand recognition of the same antigenic determinant in a peptide and in a protein. This nineteen amino acid determinant (68-87 of myohemerythrin) has been shown by several antipeptide monoclonal antibodies to be a major immunodominant site. The conformation of this determinant has been analyzed in the structure of the solved myohemerythrin structure and in solution by NMR. The main goals are to determine the following structures for a complete description of the antibody-antigen recognition. 1. Crystal structure of anti-peptide Fab. The three-dimensional structure will be determined from the currently available x-ray data quality crystals of a monoclonal Fab raised against a 19 amino acid synthetic peptide corresponding to residues 68-87 of myohemerythrin. 2. Crystal structure of an Fab-peptide complex. Crystals of the Fab will be soaked in solutions of the synthetic peptides Ka (105) and the currently available crystals grown from a mixture of the Fab and peptide will be used to determine the Fab-peptide complex structure. 3. Crystal structure of an Fab-protein. Crystallization conditions of mixtures of the anti-peptide Fab and the myohemerythrin (Ka 106-107) will be sought to obtain large single crystals of the complex. Structural studies of suitable crystals will be initiated.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
1P01GM038794-01
Application #
3941975
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037
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