Structure of the Zwit-1F beta-peptide bundle as determined by x-ray crystallography. The bundle contains eight copies of the beta-peptide Zwit-1F with parallel and antiparallel helices in like and unlike colors, respectively. Credit: Douglas S. Daniels
Schepartz and colleagues built the short protein, or peptide, from â-amino acids, which, although they exist in cells, are never found in ribosomally produced proteins. â-amino acids differ from the alpha-amino acids that compose natural proteins by the addition of a single chemical component—a methylene group—into the peptide backbone.
“The fundamental insight from this study is that â-peptides can assemble into structures that generally resemble natural proteins in shape and stability,” Schepartz said. She added that their findings about the structure of the molecule that she and her colleagues synthesized will help scientists construct more elaborate â-peptide assemblies and ones that possess true biologic function.
Schepartz and colleagues now want to try to bind metal ions to the Zwit1-F structure. Metal ion binding would enable the researchers to begin designing enzymes based on the â-peptide, she explained. “We're also interested in generating versions that can assemble in membranes, as a first step toward making transmembrane proteins composed of â-amino acids,” she said.
This paper shows that protein-like folded structures can be formed by molecules that are protein-like but have chemically distinct backbones. This is conceptually similar to recent demonstrations by Eschenmoser, Herdewijn, Benner, etc., that many nucleic acids that are chemically distinct from RNA and DNA can still form base-paired duplexes. In both cases, the implication is that biology uses its standard macromolecules not because they are uniquely suited to their tasks, but at least in part because of other considerations, such as ease of synthesis, or possibly historical accident."