Age- and diabetes-related nonenzymatic crosslinks in collagen fibrils: Candidate amino acids involved in Advanced Glycation End-products
Author(s)Gautieri, Alfonso; Redaelli, Alberto; Buehler, Markus J.; Vesentini, Simone
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Ageing and diabetes share a common deleterious phenomenon, the formation of Advanced Glycation Endproducts (AGEs), which accumulate predominantly in collagen due to its low turnover. Though the general picture of glycation has been identified, the detailed knowledge of which collagen amino acids are involved in AGEs is still missing. In this work we use an atomistic model of a collagen fibril to pinpoint, for the first time, the precise location of amino acids involved in the most relevant AGE, glucosepane. The results show that there are 14 specific lysine–arginine pairs that, due to their relative position and configuration, are likely to form glucosepane. We find that several residues involved in AGE crosslinks are within key collagen domains, such as binding sites for integrins, proteoglycans and collagenase, hence providing molecular-level explanations of previous experimental results showing decreased collagen affinity for key molecules. Altogether, these findings reveal the molecular mechanism by which glycation affects the biological properties of collagen tissues, which in turn contribute to age- and diabetes-related pathological states.
DepartmentMassachusetts Institute of Technology. Department of Civil and Environmental Engineering; Massachusetts Institute of Technology. Laboratory for Atomistic and Molecular Mechanics; Massachusetts Institute of Technology. School of Engineering
Gautieri, Alfonso, Alberto Redaelli, Markus J. Buehler, and Simone Vesentini. “Age- and Diabetes-Related Nonenzymatic Crosslinks in Collagen Fibrils: Candidate Amino Acids Involved in Advanced Glycation End-Products.” Matrix Biology 34 (February 2014): 89–95. © 2013 International Society of Matrix Biology
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