Registering alpha-helices and beta-strands using backbone C-H...O interactions

Area of Science:

• Structural biology
• Protein folding
• Biophysics

Background:

• Proteins fold into complex 3D structures essential for their function.
• Helix terminators are crucial for protein stability and defining structural boundaries.
• Short hydrogen bonds, like C-H...O, play a significant role in stabilizing protein structures.

Purpose of the Study:

• To investigate a novel helix-terminating structural motif in proteins.
• To explore the role of C-H...O interactions in protein structure stabilization.
• To understand how this motif facilitates antiparallel arrangements of helices and strands.

Main Methods:

• Analysis of a dataset of 634 high-resolution (<=2.0 A) non-homologous protein structures.
• Crystallographic characterization of a synthetic decapeptide revealing a C-H...O interaction.
• Identification and superposition of over 100 similar motifs in protein databases.
• Model building and computational studies to generate idealized alphabeta and betaalpha motifs.

Main Results:

• Discovery of a novel helix-terminating motif stabilized by C-H...O interactions.
• Identification of over 100 instances of this motif in protein structures.
• Observation that the motif can mediate antiparallel arrangements between helices and beta-strands.
• Propensity for Ser, Glu, and Gln residues at specific positions (T-4) for enhanced stabilization via side-chain-backbone interactions.

Conclusions:

• The C-H...O interaction represents a novel stabilizing force in protein structure.
• This motif provides a mechanism for registering antiparallel arrangements of helices and strands.
• The findings suggest new possibilities for designing novel protein folds and structures.