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Design and Characterization of Oligomeric bba Mini-Proteins

Mayssam H. Ali
Harvard-MIT Division of Health Sciences and Technology

Kevin A. McDonnell, Adam R. Mezo
Department of Chemistry, MIT

Barbara Imperiali
Professor of Chemistry/Biology, MIT
De novo mini-protein design is a powerful tool for the elucidation of the physical forces that determine protein structure. We have explored a series of oligomeric mini-proteins derived from the zinc finger inspired mini-protein BBA5, a twenty-three amino acid bba peptide. A shortened linker between helix and hairpin regions exposes the hydrophobic core and produces a peptide that is prone to self-association. The winning peptide from a small library was found to exist as a discrete trimer in aqueous solution. Biophysical and mutational studies have been used to characterize the trimer, and for the discovery of dimeric and tetrameric BBAs. X-ray crystallographic structural determination is ongoing, and will be of significant value in the rational design of additional oligomers of defined aggregation state.


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(last modified 3/12/03)