ADP ribosylation factor
ADP Ribosylation Factors (ARFs) are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally associate with membranes because of N-terminus myristoylation. They function as regulators of vesicular traffic and actin remodelling.
ARFs regularly associate with two types of protein, those involved in catalyzing GTP/GDP exchange, and those that serve other functions.
GTP/GDP Exchange Proteins
ARF binds to two forms of the guanosine nucleotide, guanosine triphosphate (GTP) and guanosine diphosphate (GDP). The shape of the ARF molecule is dependent upon which form it is bound to, allowing it to serve in a regulatory capacity. ARF requires assistance from other proteins in order to switch between binding to GTP and GDP. GTPase activating proteins (GAPs) force ARF to hydrolyze bound GTP to GDP, and Guanine nucleotide exchange factors force ARF to adopt a new GTP molecule in place of a bound GDP.
Other proteins interact with ARF dependent whether it is bound to GTP or GDP. The active form, ARF*GTP, binds to vesicle coat proteins and adaptors, including coat protein I COPI and various phospholipids. The inactive form is only know to bind to a class of transmembrane proteins. Different types of ARF bind specifically different kinds of effector proteins.
There are currently 6 known mammalian ARF proteins, which are divided into three classes of ARFs:
ARFs are small proteins of approximately 20 kD in size. They contain two switch regions, which change relative positions between cycles of GDP/GTP-binding. ARFs are frequently myristoylated in their N-terminal region, which contributes to their membrane association.
- Donaldson JG, Honda A (2005). "Localization and function of Arf family GTPases". Biochem. Soc. Trans. 33 (Pt 4): 639–42. doi:10.1042/BST0330639. PMID 16042562.
- Nie Z, Hirsch DS, Randazzo PA (2003). "Arf and its many interactors". Curr. Opin. Cell Biol. 15 (4): 396–404. PMID 12892779.