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News | Structural biology
An I2BC Research Team, in collaboration with the ICSN and the Ecole Polytechnique, has mapped for the first time, in man and the model plant Arabidopsis thaliana, the myristoylome, namely the whole proteins modified with a fatty acid, myristate. This modification is important because it targets these proteins to the membranes and thus contributes to their subcellular compartmentalization. These data represent an important resource, available to the community of biologists.
An organism's entire protein modification repertoire has yet to be comprehensively mapped. N-myristoylation (MYR) is a crucial eukaryotic N-terminal protein modification. Here we mapped complete Homo sapiens and Arabidopsis thaliana myristoylomes. The crystal structures of human modifier NMT1 complexed with reactive and nonreactive target-mimicking peptide ligands revealed unexpected binding clefts and a modifier recognition pattern. This information allowed integrated mapping of myristoylomes using peptide macroarrays, dedicated prediction algorithms, and in vivo mass spectrometry. Global MYR profiling at the genomic scale identified over a thousand novel, heterogeneous targets in both organisms. Surprisingly, MYR involved a non-negligible set of overlapping targets with N-acetylation, and the sequence signature marks for a third proximal acylation—S-palmitoylation—were genomically imprinted, allowing recognition of sequences exhibiting both acylations. Together, the data extend the N-end rule concept for Gly-starting proteins to subcellular compartmentalization and reveal the main neighbors influencing protein modification profiles and consequent cell fate.Read the French version.
B Castrec, C Dian, S Ciccone, CL Ebert, WV Bienvenut, JP Le Caer, JM Steyaert, C Giglione, T Meinnel. Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern. Nat. Chem. Biol. 14, 671-679 (2018)
Majeran W, Le Caer J P, Ponnala L, Meinnel T, Giglione C. Targeted profiling of A. thaliana sub-proteomes illuminates new co- and post-translationally N-terminal Myristoylated proteins. Plant Cell 30, 543-562, (2018) http://dx.doi.org/10.1105/tpc.17.00523
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.