Hydrogen bonding patterns and cooperativity in polyproline II helical bundles

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• Hydrogen bond cooperativity (HBC) is crucial for stabilizing protein secondary structures like alpha-helices and beta-sheets.
• The role of HBC in polyproline II (PPII) helices, an emerging class of protein assemblies, remains uninvestigated.

Purpose of the Study:

• To investigate the presence and role of HBC in polyproline II (PPII) helical bundles.
• To elucidate the H-bonding patterns and stabilizing mechanisms within PPII assemblies.

Main Methods:

• Computational chemistry tools and molecular modeling were employed.
• Methods were corroborated by experimental observables.
• Distinct H-bonding patterns in PPII helical bundles were characterized.

Main Results:

• HBC was found to stabilize intermolecular PPII helices, similar to amyloid fibrils.
• Both canonical (CO···HN) and non-canonical (CO···HαCα) H-bonds contribute to stabilization in Gly-rich PPII bundles.
• Non-canonical H-bonds compensate for the lack of hydrophobic cores in glycine-rich structures.

Conclusions:

• HBC is a key stabilizing factor for PPII helical bundles.
• The findings provide a mechanistic understanding of PPII bundle assembly.
• This work extends the understanding of HBC beyond canonical protein structures.