tailieunhanh - Báo cáo khoa học: Protein lipidation

Proteins are covalently modified with a variety of lipids, including fatty acids, isoprenoids, and cholesterol. Lipid modifications play important roles in the localization and function of proteins. The focus of this review is S-palmitoylation, the reversible addition of palmitate and other long-chain fatty acids to proteins at cysteine residues in a variety of sequence contexts. | ễFEBS Journal MINIREVIEW Protein lipidation Marissa J. Nadolski and Maurine E. Linder Department of Cell Biology and Physiology Washington University Schoolof Medicine St Louis MO USA Keywords DHHC-CRD fatty acylation myristoylation palmitoylation prenylation protein acyltransferase protein lipidation S-palmitoylation Ras ZDHHC Correspondence M. E. Linder Box 8228 660 S. Euclid St Louis MO 63110 USA Fax 1 314 362 7463 Tel 1 314 362 6040 E-mail mlinder@ Received 30 April 2007 revised 20 July 2007 accepted 25 July 2007 Proteins are covalently modified with a variety of lipids including fatty acids isoprenoids and cholesterol. Lipid modifications play important roles in the localization and function of proteins. The focus of this review is S-palmitoylation the reversible addition of palmitate and other long-chain fatty acids to proteins at cysteine residues in a variety of sequence contexts. The functional consequences of palmitoylation are diverse. Palmi-toylation facilitates the association of proteins with membranes mediates protein trafficking and more recently has been appreciated as a regulator of protein stability. Members of a family of integral membrane proteins that harbor a DHHC cysteine-rich domain mediate most cellular palmitoy-lation events. Here we focus on DHHC proteins that modify Ras proteins in yeast and mammalian cells. doi Introduction Proteins are covalently modified with lipids through multiple mechanisms. Lipid modifications can be broadly divided into two categories those that occur in the cytoplasm or on the cytoplasmic face of membranes and those that occur in the lumen of the secretory pathway. Three common lipid modifications that occur in the cytoplasm are N-myristoylation S-palmi-toylation and prenylation Fig. 1 . N-myristoylation is the covalent addition of the fatty acid myristate to an N-terminal glycine residue via an amide linkage 1 . Prenylation is the addition of an isoprenoid