Side-chain structures in the first turn of the alpha-helix

Area of Science:

• Protein structure and dynamics
• Biophysics
• Structural biology

Background:

• Alpha-helices are fundamental protein structures.
• The N-terminus of alpha-helices exhibits unique structural and chemical properties.
• Understanding these terminal regions is crucial for predicting protein folding and function.

Purpose of the Study:

• To investigate amino acid and side-chain preferences at the N1, N2, and N3 positions of alpha-helices.
• To identify hydrogen-bonding patterns and their influence on N-terminal residue preferences.
• To determine if these terminal preferences differ from those within helix interiors.

Main Methods:

• Analysis of 2102 alpha-helix N-termini from 298 high-resolution protein crystal structures.
• Characterization of amino acid and side-chain rotamer propensities at N1, N2, and N3.
• Mapping of backbone and side-chain hydrogen-bonding interactions.

Main Results:

• Strong, unique structural preferences were identified at N1, N2, and N3 positions.
• Rotamer distributions are influenced by amino acid identity and hydrogen-bonding to backbone NH groups.
• Specific side-chain interactions (e.g., Arg(N-cap) to Asp(N2)) were observed.
• "Good N2" residues preferentially form backbone hydrogen bonds, sometimes hindered by N-caps.

Conclusions:

• The N-terminus of alpha-helices exhibits distinct energetic and structural preferences.
• These preferences are significantly different from those found in helix interiors.
• N-terminal helical sites (N1, N2, N3) warrant explicit consideration in studies of protein and peptide helical structure.