Synergistic sequence contributions bias glycation outcomes

Joseph M. McEwen, Sasha Fraser, Alexxandra L. Sosa Guir, Jaydev Dave and Rebecca A. Scheck ()
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Joseph M. McEwen: Tufts University
Sasha Fraser: Tufts University
Alexxandra L. Sosa Guir: Tufts University
Jaydev Dave: Tufts University
Rebecca A. Scheck: Tufts University

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract The methylglyoxal-derived hydroimidazolone isomer, MGH-1, is an abundant advanced glycation end-product (AGE) associated with disease and age-related disorders. As AGE formation occurs spontaneously and without an enzyme, it remains unknown why certain sites on distinct proteins become modified with specific AGEs. Here, we use a combinatorial peptide library to determine the chemical features that favor MGH-1. When properly positioned, tyrosine is found to play an active mechanistic role that facilitates MGH-1 formation. This work offers mechanistic insight connecting multiple AGEs, including MGH-1 and carboxyethylarginine (CEA), and reconciles the role of negative charge in influencing glycation outcomes. Further, this study provides clear evidence that glycation outcomes can be influenced through long- or medium-range cooperative interactions. This work demonstrates that these chemical features also predictably template selective glycation on full-length protein targets expressed in mammalian cells. This information is vital for developing methods that control glycation in living cells and will enable the study of glycation as a functional post-translational modification.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23625-8

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DOI: 10.1038/s41467-021-23625-8

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