The long term aim of this project is to understand the recognition, interactions and assembly of immunologically important macromolecules. The first major goal is to understand the dual recognition of synthetic peptide sequence and a secondary goal is to investigate how an antibody can accommodate different peptide antigens. In this way the conformations of different peptide sequences will also be determined complexed to the Fab and allow correlation of sequence and structure with antibody specificity. The second major goal is to understand the recognition of a human lymphokine and its T-cell receptor. More specifically, this project aims at the characterization of the molecular basis for the binding of the critically important human T-cell growth factor interleukin-2 (IL-2) with the p55 (Tac) component of the high affinity IL-2 receptor (IL-2R). The determination of the three-dimensional structure of IL-2 and the p55 IL-2R individually as well as that of a receptor/ligand complex will be valuable for a better understanding of the mechanism of formation of both low and high affinity IL-2 receptors, as well as that of the transduction of this binding event into a physiological response by target cells and of the regulation of this process. The additional study of IL-2 mutants and the p75 receptor should provide additional insights into the structure and biological functions of IL-2 and its receptors. The following are the specific aims: (1)Crystal Structures of Fab-Peptide Complexes (2)Crystal Structure of an Fab-Protein Complex (3)Crystal Structure of Interleukin-2 (IL-2) (4)Crystal Structure of IL-2/IL-2 Receptor Complexes (5)Crystal Structure of the p55 IL-2 Receptor The structures will be solved by x-ray crystallography using either isomorphous replacement (multiple or single) or molecular replacement (MR) methods. The use of Fabs in the crystallization of IL-2 and its p55 receptors should facilitate the structure determination using MR methods. Data collection with multiwire detectors and image plates is proposed with either conventional x-ray sources or synchrotron radiation.
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| Wilson, I A; Stanfield, R L; Jewell, D A et al. (1994) Immune recognition of viral antigens. Infect Agents Dis 3:155-62 |
