Histidine-Mediated pH-Sensitive Regulation of M-Ficolin: GlcNAc Binding Activity in Innate Immunity Examined by Molecular Dynamics Simulations
2011
pH-Sensitive Regulation of M-Ficolin: GlcNAc Binding Activity in Innate Immunity Examined by Molecular Dynamics Simulations
publication
Evidence: moderate
Author Information
Author(s): Yang Lifeng, Zhang Jing, Ho Bow, Ding Jeak Ling
Primary Institution: Computational and Systems Biology, Singapore-MIT Alliance (SMA)
Hypothesis
The study investigates how pH affects the binding activity of M-ficolin to GlcNAc through conformational changes.
Conclusion
The study found that the binding of GlcNAc to M-ficolin is regulated by pH-dependent conformational changes in the protein.
Supporting Evidence
- The pH-sensitive binding of GlcNAc is regulated by a conformational equilibrium between the active and inactive states of M-ficolin.
- Constant pH MD simulation indicated that the cis active isomer of Asp282-Cys283 peptide bond was predominant around neutral pH.
- The protonation of His284 was found to be associated with the trans-to-cis isomerization of Asp282-Cys283 peptide bond.
Takeaway
M-ficolin is like a key that can change shape depending on the pH, which helps it decide when to grab onto a sugar from germs or dead cells.
Methodology
The study used constant pH molecular dynamics simulations to analyze the pH effects on the M-ficolin protein structure and its binding to GlcNAc.
Digital Object Identifier (DOI)
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