What question did this study set out to answer?

Investigate whether advanced lipoxidation end products derived from reactive carbonyl species bind the RAGE receptor and elucidate the molecular mechanisms controlling this interaction.

December 18, 2018Redox BiologyOpen Access

Advanced lipoxidation end products (ALEs) as RAGE binders: Mass spectrometric and computational studies to explain the reasons why

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Investigate whether advanced lipoxidation end products derived from reactive carbonyl species bind the RAGE receptor and elucidate the molecular mechanisms controlling this interaction.
Generated advanced lipoxidation end products in vitro by incubating human serum albumin with 4-hydroxy-trans-2-nonenal, acrolein, and malondialdehyde, followed by mass spectrometric identification.
Assessed binding affinity using a pull-down assay targeting the VC1 ligand-binding domain of RAGE and performed computational modeling to examine structural determinants of the interaction.
Confirmed that lipid peroxidation-derived advanced lipoxidation end products bind the VC1 domain of RAGE.
Demonstrated that adducts such as dihydropyridine-lysine, N-2-pyrimidyl-ornithine, and FDPK reduce target amino acid basicity to a neutral state at physiological conditions.
Showed that neutralization of modified residues disrupts local ion-pairs, enabling neighboring acidic residues to interact directly with positively charged residues on RAGE.

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Implication

In vitro and computational study uncovers advanced lipoxidation end products as RAGE binders via basicity reduction, indicating a structural basis for lipid-driven inflammation.

Cite This Study

Mol et al. (2018) studied this question.

synapsesocial.com/papers/6a89b13c5edafe343d92f11c https://doi.org/10.1016/j.redox.2018.101083

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Implication

In vitro and computational study uncovers advanced lipoxidation end products as RAGE binders via basicity reduction, indicating a structural basis for lipid-driven inflammation.

Advanced lipoxidation end products (ALEs) as RAGE binders: Mass spectrometric and computational studies to explain the reasons why

Key Points

Discussion

Implication

Cite This Study

Advanced lipoxidation end products (ALEs) as RAGE binders: Mass spectrometric and computational studies to explain the reasons why

Key Points

Discussion

Implication

Cite This Study

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