Open-and-shut cases in coiled-coil assembly: alpha-sheets and alpha-cylinders

Area of Science:

• Protein structure and folding
• Bioinformatics and computational biology

Background:

• Coiled coils are common protein motifs formed by alpha-helices.
• Heptad repeats in sequences dictate the formation of amphipathic alpha-helices.
• The 'knobs-into-holes' packing model describes hydrophobic interactions in coiled coils.

Purpose of the Study:

• To develop software (SOCKET) for recognizing 'knobs-into-holes' packing in protein structures.
• To investigate the role of multiple, offset heptad repeats in coiled-coil assembly.
• To classify coiled-coil structures into alpha-sheets and alpha-cylinders based on heptad repeat arrangements.

Main Methods:

• Development of the SOCKET software for analyzing protein structures.
• Trawling the protein data bank to identify coiled-coil structures.
• Analysis of sequence offsets in heptad repeats to correlate with oligomeric state.

Main Results:

• Identified canonical coiled coils with single heptad repeats.
• Discovered structures with multiple, overlapping heptad repeats, extending existing models.
• Found that the sequence offset of heptad repeats relates to coiled-coil oligomerization.
• Characterized two distinct multihelix assembly types: alpha-sheets and alpha-cylinders, based on heptad repeat arrangements.

Conclusions:

• Multiple, offset heptad repeats are key to understanding assemblies of more than two helices.
• The specific offset of heptad repeats determines whether alpha-sheets or alpha-cylinders are formed.
• The SOCKET software provides a tool for identifying and classifying coiled-coil structures.