Post-translational myristoylation: Fat matters in cellular life and death

Regulatory Subunit Myristoylation Antagonizes Calcineurin Phosphatase Activation in Yeast

“…Closer examination of the Cnb1 sequence revealed that Ser-6 (underlined) is located within the Cnb1 myristoylation consensus site Met-Gly-X-X-X-Ser-X-X-X. N-Myristoylation refers to the covalent attachment of myristate, a short 14-carbon fatty acid, to the amino-terminal glycine residue following removal of the initiating methionine residue during protein translation (30,31). Myristoylation of CNB is conserved from yeast to humans (28,32), but a functional consequence of this modification had not previously been reported.…”

The Protein Lipidation and Its Analysis

“…The attachment of the saturated 14-carbon myristic acid to a N-terminal glycine via an amide bond, after cleavage of the initiating methionine, is known as N-myristoylation and is catalysed by a N-myristoyl transferase (NMT) [30] (for more information on this lipid modification the reader is referred to a recent excellent review by Berthiaume and co-workers on protein myristoylation [10]). NMT recognizes a general consensus sequence for myristoylation (Gly-X-X-X-(Ser/Thr/Cys)) containing a N-terminal glycine, 3 other amino acids and a serine, threonine or a cysteine in the fifth position.…”

“…However, the significance of the high diversity in lipid modifications as well as the mechanism by which lipidation controls function and activity remains poorly understood. Furthermore, misregulation has been often encountered in diseases [9,10]. Hence, lipidated proteins are crucial for bacterial, viral and parasite infection processes [10] and alterations in the lipidation pattern of membrane associated proteins have been detected in cancer [11,12] as well as in neurological disorders [13].…”

“…Furthermore, misregulation has been often encountered in diseases [9,10]. Hence, lipidated proteins are crucial for bacterial, viral and parasite infection processes [10] and alterations in the lipidation pattern of membrane associated proteins have been detected in cancer [11,12] as well as in neurological disorders [13]. For all these reasons, the development of strategies enabling the study of known and new posttranslational modifications and especially of the dynamic changes of the reversible palmitoylation would be of great interest.…”

A component of the mitochondrial outer membrane proteome of T. brucei probably contains covalent bound fatty acids

“…There are many different ways of how proteins can be acylated; among them the covalent modification of an N-terminal glycine residue with myristate (a 14-carbon chain fatty acid) probably represents the best-characterized protein fatty acid modification. Proteins with the N-terminal consensus sequence MGXXXS/T (Maurer-Stroh et al, 2010a;Maurer-Stroh et al, 2010b;Towler et al, 1988) are subject to this irreversible modification, which is carried out by the enzyme myristoyl-CoA:protein N-myristoyltransferase (NMT) (Bhatnager et al, 1999;Farazi et al, 2001), usually in a co-translational fashion (Martin et al, 2011). Whereas myristoylation of a protein increases its hydrophobicity and thus its membrane affinity, this single acylation is considered insufficient for anchoring a protein stably to a membrane (Peitzsch and McLaughlin, 1993).…”