Importance of the Subunit-Subunit Interface in Ferritin Disassembly: A Molecular Dynamics Study

Area of Science:

• Biochemistry
• Structural Biology
• Protein Dynamics

Background:

• Ferritin's cage-like structure facilitates particle loading for diverse applications.
• The precise mechanism of ferritin disassembly, particularly its pH-dependent behavior, remains incompletely understood.

Purpose of the Study:

• To investigate the impact of pH on ferritin interfaces and stability.
• To elucidate the mechanism of ferritin disassembly under acidic conditions using molecular dynamics simulations.

Main Methods:

• Conducting molecular dynamics (MD) simulations at various pH values.
• Analyzing inter-subunit interfaces and their stability within the ferritin structure.

Main Results:

• Ferritin dimers exhibit stability even at pH 2.0, identifying them as key disassembly subunits.
• Monomer rotation within dimers causes slight swelling, initiating the disassembly process.
• The interface between ferritin dimers is critical, with protonation at low pH disrupting salt bridges and hydrogen bonds, leading to disassembly.

Conclusions:

• The study reveals a pH-dependent mechanism for ferritin disassembly in acidic environments.
• Understanding these forces aids in designing functional ferritin cages for specific applications.