The Rippled Beta-Sheet: An Old Prediction Inspires a New Field.

Area of Science:

• Structural biology
• Biophysics
• Peptide chemistry

Background:

• The rippled β-sheet motif was theoretically proposed in 1953 but remained largely unexplored for decades.
• Unlike the well-established pleated β-sheet, experimental evidence for the rippled β-sheet's structural viability emerged significantly later, primarily in the 21st century.

Purpose of the Study:

• To provide the first experimental crystal structure of a rippled β-sheet.
• To explore the formation and properties of rippled β-sheets using designed peptide sequences.
• To investigate the potential of rippled β-sheets as a platform for diverse peptidic folds.

Main Methods:

• Crystal structure determination of a rippled β-sheet.
• Design and synthesis of model tripeptides and longer peptide sequences.
• Rational molecular design of self-rippling peptides and macrocycles.

Main Results:

• The first crystal structure of a rippled β-sheet was reported 69 years after its prediction.
• Demonstrated the formation of rippled sheets from various designed peptide sequences, including self-rippling peptides and macrocycles.
• Observed over half of the canonical amino acids within the rippled β-sheet structure, indicating broad applicability.

Conclusions:

• The rippled β-sheet is a structurally viable and versatile motif with significant potential.
• The ability to form diverse aggregated peptidic folds from rippled sheets offers unique properties for future applications.
• The field of rippled β-sheet research is rapidly advancing, with ample opportunities for further discovery.