5O9S

HsNMT1 in complex with CoA and Myristoylated-GKSNSKLK octapeptide

Summary for 5O9S

• Entry DOI: 10.2210/pdb5o9s/pdb
• Descriptor: Glycylpeptide N-tetradecanoyltransferase 1, Neuronal calcium sensor 1, GLYCEROL, ... (6 entities in total)
• Functional Keywords: transferase, glycylpeptide n-tetradecanoyltransferase 1 n-myristoyltransferase 1, n-myristoyltransferase type1, nmt1, nmt, acyltransferase, myr-peptide, coa, myr-coa, myristoyl, gnat
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 95590.35

Authors

Dian, C.,Meinnel, T.,Giglione, C. (deposition date: 2017-06-20, release date: 2018-06-27, Last modification date: 2024-10-23)

Primary citation

Castrec, B.,Dian, C.,Ciccone, S.,Ebert, C.L.,Bienvenut, W.V.,Le Caer, J.P.,Steyaert, J.M.,Giglione, C.,Meinnel, T.
Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern.
Nat. Chem. Biol., 14:671-679, 2018

PubMed Abstract: 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.

PubMed: 29892081
DOI: 10.1038/s41589-018-0077-5

Experimental method

X-RAY DIFFRACTION (2.7 Å)