The reaction of free amino groups in proteins with reactive carbonyl species, known as glycation, leads to the formation of mixtures of products, collectively referred to as advanced glycation endproducts (AGEs). These compounds have been implicated in several important diseases, but their role in pathogenesis and clinical symptoms’ development is still debated. Particularly, AGEs are often associated to the formation of amyloid deposits in conformational diseases, such as Alzheimer’s and Parkinson’s disease, and it has been suggested that they might influence the mechanisms and kinetics of protein aggregation. We here present the characterization of the products of glycation of the model protein MNEI with methylglyoxal and their effect on the protein structure. We demonstrate that, despite being an uncontrolled process, glycation occurs only at specific residues of the protein. Moreover, while not affecting the protein fold, it alters its shape and hydrodynamic properties and increases its tendency to fibrillar aggregation. Our study opens the way to in deep structural investigations to shed light on the complex link between protein post-translational modifications, structure, and stability.

Structural effects of methylglyoxal glycation, a study on the model protein MNEI

Leone, Serena;Melchiorre, Chiara;Carpentieri, Andrea;Picone, Delia
2019

Abstract

The reaction of free amino groups in proteins with reactive carbonyl species, known as glycation, leads to the formation of mixtures of products, collectively referred to as advanced glycation endproducts (AGEs). These compounds have been implicated in several important diseases, but their role in pathogenesis and clinical symptoms’ development is still debated. Particularly, AGEs are often associated to the formation of amyloid deposits in conformational diseases, such as Alzheimer’s and Parkinson’s disease, and it has been suggested that they might influence the mechanisms and kinetics of protein aggregation. We here present the characterization of the products of glycation of the model protein MNEI with methylglyoxal and their effect on the protein structure. We demonstrate that, despite being an uncontrolled process, glycation occurs only at specific residues of the protein. Moreover, while not affecting the protein fold, it alters its shape and hydrodynamic properties and increases its tendency to fibrillar aggregation. Our study opens the way to in deep structural investigations to shed light on the complex link between protein post-translational modifications, structure, and stability.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/751109
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