What type of bond formation occurs in myristoylation?
Myristoylation represents cotranslational irreversible lipidation catalyzed by cytosolic N-myristoyltransferases NMT1 and NMT2. After methionine aminopeptidase removes initiator methionine, glycine at position two becomes exposed as acceptor. NMT binds myristoyl-CoA, a fourteen-carbon saturated fatty acyl thioester, and transfers acyl chain to alpha-amino group of N-terminal glycine forming stable amide linkage resistant to neutral hydroxylamine, alkaline treatment, and reducing agents, unlike labile thioesters. The myristate provides approximately eight kilocalories per mol hydrophobic insertion energy insufficient alone for permanent anchoring, so second signals are required including polybasic cluster that binds acidic phospholipids or secondary palmitoylation of adjacent cysteines. Consensus sequence MGXXXS/T directs recognition for substrates like Src family kinases, ADP-ribosylation factor, G-alpha i subunits, and MARCKS. Myristate targets proteins to cytosolic leaflet microdomains regulating membrane-cytosol shuttling, signal transduction, vesicular trafficking and oncogenic transformation with high membrane specificity. Additional regulation involves myristoyl electrostatic switch where calcium binding exposes myristate in recoverin and MARCKS modulating membrane binding cycles.
Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 10, Protein Lipidation and Myristoylation.