Functional hypothesis on miraculin' sweetness by a molecular dynamics approach

Area of Science:

• Biochemistry
• Molecular Biology
• Sensory Science

Background:

• Miraculin is a unique taste-modifying protein that converts sourness into sweetness.
• Its activity is pH-dependent, with optimal function at acidic pH (around 3.0).
• Two histidine residues (His) have been previously implicated in miraculin's taste-modifying properties.

Purpose of the Study:

• To investigate the structural and functional roles of two specific histidine residues (H29 and H59) in miraculin.
• To understand how these residues contribute to the protein's activity at different pH levels.
• To explore the dimer arrangement and conformational changes of wild-type and mutated miraculin.

Main Methods:

• Molecular dynamics (MD) simulations were performed on wild-type miraculin and three mutants (H29A, H59A, H29A/H59A).
• Simulations were conducted at both neutral and acidic pH conditions.
• Analysis focused on dimer stability, inter-chain disulfide bonds, and monomer conformational changes.

Main Results:

• At acidic pH, charged histidine residues at the dimer interface induced structural rearrangements, leading to monomer opening and receptor adaptation.
• Mutant dimers (H29A, H59A, H29A/H59A) exhibited a closed conformation.
• Histidine 29 (H29) plays a critical role in dimer stabilization/destabilization, with a cooperative effect observed between H29 and H59.

Conclusions:

• The study elucidates the critical role of histidine residues in mediating pH-dependent structural changes of miraculin dimers.
• These conformational shifts are essential for miraculin's taste-modifying activity.
• The findings provide insights into the molecular mechanisms underlying taste perception and protein function.