Pitch diversity in alpha-helical coiled coils

Area of Science:

• Biophysics
• Structural Biology
• Protein Science

Background:

• Alpha-helical coiled coils are common protein structures.
• Understanding their local conformation and pitch is crucial for function.
• Existing methods may not fully capture local structural nuances.

Purpose of the Study:

• To develop and apply novel methods for measuring local pitch in alpha-helical coiled coils.
• To investigate the relationship between residue composition and local pitch.
• To assess the utility of these methods for analyzing protein structures and dynamics.

Main Methods:

• Development of two complementary methods for measuring local pitch based on heptad position.
• Application of these methods to analyze six crystal structures of coiled coils.
• Utilizing molecular dynamics simulations for the GCN4 leucine zipper.

Main Results:

• Identified diverse pitch values: ~150 Å for two-stranded and ~200 Å for three- and four-stranded coiled coils.
• Demonstrated that polar/charged residues in the apolar interface significantly affect local pitch.
• Correlated local pitch changes with skip residues (heptad frame shifts) in viral proteins like influenza HA.
• Showed excellent agreement between predicted and crystal structure local pitch for GCN4 leucine zipper.

Conclusions:

• The developed methods provide sensitive insights into local coiled-coil conformation.
• Local pitch is influenced by residue type and can indicate coiled-coil stability.
• These techniques offer valuable tools for analyzing coiled-coil structures, including fibrous proteins and viral glycoproteins, potentially revealing details missed by global analyses.