New Research Confirms ‘Rippled Sheet’ Protein Construction Predicted In 1953

An uncommon protein construction often known as a “rippled beta sheet,” first predicted in 1953, has now been created within the laboratory and characterised intimately utilizing x-ray crystallography.

The brand new findings, revealed in July in Chemical Science, might allow the rational design of distinctive supplies primarily based on the rippled sheet structure.

“Our examine establishes the rippled beta sheet layer configuration as a motif with basic options and opens the street to structure-based design of distinctive molecular architectures, with potential for supplies growth and biomedical purposes,” stated Jevgenij Raskatov, affiliate professor of chemistry and biochemistry at UC Santa Cruz and corresponding writer of the paper.

Proteins are available in an unlimited vary of styles and sizes to hold out their myriad structural and practical roles in dwelling cells. Sure widespread structural motifs, such because the alpha helix, are discovered in lots of protein buildings.

The rippled sheet is a variation on the pleated beta sheet, a widely known structural motif present in 1000’s of proteins. Linus Pauling and Robert Corey described the rippled beta sheet in 1953, two years after introducing the idea of the pleated beta sheet. Whereas the pleated beta sheet is well-known and sometimes known as merely the beta sheet, the rippled sheet remained a largely theoretical construction for many years.

In a earlier examine revealed in 2021, Raskatov’s workforce reported acquiring a rippled beta sheet construction by mixing a small peptide with equal quantities of its mirror picture. The researchers used mirror-image types of triphenylalanine, a brief peptide consisting of three phenylalanine amino acids. The mirror-image peptides joined in pairs to type “dimers” with the expected construction, however they didn’t type the prolonged, periodic rippled beta-sheet layer topography hypothesized by Pauling and Corey.

“The dimers packed collectively into herringbone layer buildings, which raised doubt as as to whether the periodic rippled beta-sheet layer configuration was viable,” Raskatov stated.

Within the new examine, the researchers substituted different amino acids for one of many triphenylalanines to create barely completely different tripeptides and their mirror-images. Utilizing these new tripeptides, they have been in a position to create three completely different aggregating peptide methods that fashioned prolonged antiparallel rippled beta sheet layers, by which mirror-image peptide strands have been organized in alternating style. The outcomes of x-ray crystallography confirmed that the crystal buildings are in wonderful general settlement with the predictions made by Pauling and Corey.

The co-first authors of the paper are Amaruka Hazari, a workers scientist in Raskatov’s lab, and Michael Sawaya at UCLA. Different coauthors embody Timothy Johnstone at UC Santa Cruz and Niko Vlahakis, David Boyer, Jose Rodriguez, and David Eisenberg at UCLA. This work was supported by the Nationwide Institutes of Well being.

College of California – Santa Cruz

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