NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle.

Autor: Kosciuk T; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., Price IR; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., Zhang X; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., Zhu C; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., Johnson KN; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., Zhang S; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.; Howard Hughes Medical Institute; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., Halaby SL; Department of Molecular Biology and Genetics; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, 14853, USA., Komaniecki GP; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., Yang M; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA., DeHart CJ; National Resource for Translational and Developmental Proteomics, Departments of Chemistry and Molecular Biosciences and the Feinberg School of Medicine, Northwestern University, Evanston, IL, 60208, USA., Thomas PM; National Resource for Translational and Developmental Proteomics, Departments of Chemistry and Molecular Biosciences and the Feinberg School of Medicine, Northwestern University, Evanston, IL, 60208, USA., Kelleher NL; National Resource for Translational and Developmental Proteomics, Departments of Chemistry and Molecular Biosciences and the Feinberg School of Medicine, Northwestern University, Evanston, IL, 60208, USA., Fromme JC; Department of Molecular Biology and Genetics; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, 14853, USA., Lin H; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA. hl379@cornell.edu.; Howard Hughes Medical Institute; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA. hl379@cornell.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Feb 26; Vol. 11 (1), pp. 1067. Date of Electronic Publication: 2020 Feb 26.
DOI: 10.1038/s41467-020-14893-x
Abstrakt: Lysine fatty acylation in mammalian cells was discovered nearly three decades ago, yet the enzymes catalyzing it remain unknown. Unexpectedly, we find that human N-terminal glycine myristoyltransferases (NMT) 1 and 2 can efficiently myristoylate specific lysine residues. They modify ADP-ribosylation factor 6 (ARF6) on lysine 3 allowing it to remain on membranes during the GTPase cycle. We demonstrate that the NAD + -dependent deacylase SIRT2 removes the myristoyl group, and our evidence suggests that NMT prefers the GTP-bound while SIRT2 prefers the GDP-bound ARF6. This allows the lysine myrisotylation-demyristoylation cycle to couple to and promote the GTPase cycle of ARF6. Our study provides an explanation for the puzzling dissimilarity of ARF6 to other ARFs and suggests the existence of other substrates regulated by this previously unknown function of NMT. Furthermore, we identified a NMT/SIRT2-ARF6 regulatory axis, which may offer new ways to treat human diseases.
Databáze: MEDLINE
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