A crystal-structural study of Pauling-Corey rippled sheets.

Area of Science:

• Structural biology
• Biochemistry
• Molecular modeling

Background:

• The rippled β-sheet, a protein secondary structure, was theoretically proposed in 1953 but has lacked experimental structural validation.
• Unlike the common pleated β-sheet, rippled β-sheets involve interacting β-strands of opposite chirality (mirror-images).
• Previous research on rippled sheets focused on racemic peptide aggregation, with limited structural insights.

Purpose of the Study:

• To provide high-resolution crystal structures of rippled β-sheets.
• To validate theoretical predictions of rippled sheet formation.
• To inform the rational design of novel rippled sheet architectures.

Main Methods:

• X-ray crystallography to determine the high-resolution structure of triphenylalanine-based rippled sheets.
• Molecular modeling to compare experimental structures with theoretical predictions.
• Protein Data Bank (PDB) mining to identify naturally occurring rippled sheets in protein structures.

Main Results:

• A high-resolution crystal structure of (l,l,l)-triphenylalanine and (d,d,d)-triphenylalanine forming dimeric antiparallel rippled sheets was determined.
• These dimeric sheets pack into herringbone layer structures, consistent with Pauling and Corey's 1953 theoretical predictions.
• Three instances of rippled sheets were identified within existing racemic protein crystal structures in the PDB.

Conclusions:

• The crystal structure provides the first direct experimental evidence for the formation of rippled β-sheets.
• The findings validate decades-old theoretical models and offer a foundation for designing new peptide and protein architectures.
• The identification of naturally occurring rippled sheets suggests their potential biological relevance.