High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2020

High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation

Pierre Legrand
Mengjie Shen
  • Fonction : Auteur

Résumé

The promising drug target N-myristoyltransferase (NMT) catalyses an essential protein modification thought to occur exclusively at N-terminal glycines (Gly). Here, we present high-resolution human NMT1 structures co-crystallised with reactive cognate lipid and peptide substrates, revealing high-resolution snapshots of the entire catalytic mechanism from the initial to final reaction states. Structural comparisons, together with biochemical analysis, provide unforeseen details about how NMT1 reaches a catalytically competent conformation in which the reactive groups are brought into close proximity to enable catalysis. We demonstrate that this mechanism further supports efficient and unprecedented myristoylation of an N-terminal lysine side chain, providing evidence that NMT acts both as N-terminal-lysine and glycine myristoyltransferase.
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Dates et versions

hal-02502311 , version 1 (10-11-2020)

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Citer

Cyril Dian, Inmaculada Pérez-Dorado, Frédéric Rivière, Thomas Asensio, Pierre Legrand, et al.. High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation. Nature Communications, 2020, 11 (1), pp.1132. ⟨10.1038/s41467-020-14847-3⟩. ⟨hal-02502311⟩
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