Targeting proteins to plasma membrane and membrane microdomains by N-terminal myristoylation and palmitoylation

Abstract

This chapter discusses the use of N-terminal fatty acylation sequences for targeting chimeric proteins to the plasma membrane.. The fatty acids myristate and palmitate are covalently linked to a wide variety of viral and cellular proteins. Sequence motifs located at the N terminus are responsible for conferring N-myristoylation of all known N-myristoylated proteins. In addition, signals for protein palmitoylation are often located at or near the N terminus. Many myristoylated proteins and nearly all dually fatty acylated proteins are attached to the inner leaflet of the cell plasma membrane. The N-terminal sequence motifs that direct fatty acylation have been shown to be both necessary and sufficient for conferring plasma membrane association. In addition to providing plasma membrane binding, palmitoylated sequences have been shown to confer targeting of proteins to specific plasma membrane microdomains The chapter describes the three general types of N-terminal fatty acylation motifs that are known to confer membrane binding. Type 1 motifs contain a “myristate plus basic” signal. These proteins are modified by covalent attachment of the 1Ccarbon fatty acid myristate to the N-terminal glycine residue. On the other hand, Type 2 and 3 N-terminal motifs are useful for conferring plasma membrane microdomain localization to proteins.