Poly-γ-glutamylation of biomolecules

Poly-γ-glutamylation of biomolecules

Poly-γ-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates and F 420 . Despite decades of research, key mechanistic questions remain as to how enzymes successively add glutamates to poly-γ-glutamate chains while maintaining cofactor speci...

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Bibliographic Details
Published in:Nature communications Vol. 15; no. 1; p. 1310
Main Authors: Bashiri, Ghader, Bulloch, Esther M. M., Bramley, William R., Davidson, Madison, Stuteley, Stephanie M., Young, Paul G., Harris, Paul W. R., Naqvi, Muhammad S. H., Middleditch, Martin J., Schmitz, Michael, Chang, Wei-Chen, Baker, Edward N., Squire, Christopher J.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12-02-2024
Nature Publishing Group
Nature Portfolio
Subjects:
631/45/173
631/45/535/1266
631/45/607
82/16
82/29
82/58
82/6
82/80
82/83
Archaea
Biomolecules
Cofactors
Enzymes
Folic acid
Folylpolyglutamate synthase
Glutamates
Glutamic acid
Humanities and Social Sciences
multidisciplinary
Science
Science (multidisciplinary)
Species diversity
Substrate specificity
Substrates
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Summary:Poly-γ-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates and F 420 . Despite decades of research, key mechanistic questions remain as to how enzymes successively add glutamates to poly-γ-glutamate chains while maintaining cofactor specificity. Here, we show how poly-γ-glutamylation of folate and F 420 by folylpolyglutamate synthases and γ-glutamyl ligases, non-homologous enzymes, occurs via processive addition of L -glutamate onto growing γ-glutamyl chain termini. We further reveal structural snapshots of the archaeal γ-glutamyl ligase (CofE) in action, crucially including a bulged-chain product that shows how the cofactor is retained while successive glutamates are added to the chain terminus. This bulging substrate model of processive poly-γ-glutamylation by terminal extension is arguably ubiquitous in such biopolymerisation reactions, including addition to folates, and demonstrates convergent evolution in diverse species from archaea to humans. Poly-γ-glutamate tails are a distinctive feature of folate and F 420 cofactors, but it was unclear how these tails elongate while maintaining substrate specificity. Here, the authors discover that folylpolyglutamate synthase and γ-glutamyl ligase enzymes add successive L -glutamates to the termini of the growing γ-glutamyl chain in a processive mechanism.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-45632-1