GLYCATION OF LYSOZYME PROVIDES NEW MECHANISTIC INSIGHTS IN DIABETES-RELATED PROTEIN AGGREGATION

Glycation of proteins occurs in vivo as a result of their non-enzymatic reaction with carbohydrates (and/or their autoxidation products). Protein glycation can cause loss-of-function and can also promote protein aggregation, which could explain the observed link between hyperglycaemia and the higher prevalence of aggregating diseases in diabetic people.

 

Since the exact molecular mechanism that connects glycation with aggregation remains to be discovered, we have applied an interdisciplinary approach to study the non-enzymatic glycation of hen egg white lysozyme (HEWL) with ribose and glycolaldehyde as glycating agents. By combining a broad range of techniques (e.g. chromatography, fluorescence CD, NMR, FTIR, SAXS, AFM and MALDI-TOF mass spectrometry, etc..) we identified the formation of Advanced Glycation End Products (AGEs) and assessed their effect on the protein structure. We found that alterations of the surface hydrophobicity of HEWL can trigger protein aggregation through the formation of small aggregated particles, which are analyzed in detail in comparison to native HEWL and the notorious amyloid fibers. By comparing the effects of 2 different glycating agents, our work showcases mechanistic similarities and differences within two different glycation processes that can occur on the same model protein. The new insights contribute toward a better understanding of the link between glycation and aggregation.

Authors

Kris Pauwels(1,2)
Laura Mariño(3,4)
Pilar Sanchis(3,4,5)
Bartolomé Villanova(3,4)
Pierre Lebrun(1,2)
Juan Frau(3,4)
Josefa Donoso(3,4)
Miquel Adrover(3,4)

Organisations

VIB Centre for Structural Biology, VIB, Brussels, Belgium (1)
Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium (2)
University Institute of Health Sciences, Palma de Mallorca, Spain (3)
Departament de Química, Universitat de les Illes Balears, Palma de Mallorca, Spain (4)
Research Unit of Son Llatzer Hospital, Palma de Mallorca, Spain (5)

Presenting author

Kris Pauwels, FWO postdoctoral researcher, VIB-VUB Centre for Structural Biology
Kris.Pauwels@vub.be
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