Function

There are three essential functional components of ADP-Ribosylation Factor 1: membrane affinity, nucleotide-induced conformational changes; and effector interactions. It is involoved in membrane affinity because it plays a major role in the vesicular transport between the ER and the Golgi Apparatus. It plays an important role in the formation of non-clatherin and clatherin coated vesicles which are used in the transportation of vesicles, which carry important cellular components meeded in processes such as cell signalling. It uses its positive residues on its side chains to associate with the membrane of Golgi.

The positive residues become exposed when the ARF-GDP is unbound and the GTP is able to bind to the ARF. The hydrolysis of GTP is mediatated by ARF. The binding of GTP to ARF induces a conformational change which mediates the membrane localization. It is also important for the GTP-dependent ARF to by myristoylated in order for the GTP to bind. The ADP-GTP conformational form is only stable when interacting with the membranes.

ARF also acts as an effector of certain interactions like that of cholera toxin and phospholipase D. Cholera toxin, CTA, is a secretory product that is responsible for the devastating diarrheal syndrome characteristics of cholera. This happens by cholera toxins exerting its effects on intestinal cells by ADP-Ribosylation of the alpha-subunit of a heterotrimeric guanine nucleotide-binding (G) protein that is the stimulatory G protein of adenylyl cyclase that acts as a signal transducing element from surface receptors to intracellular effectors. CTA also needs the presenece of phospholipids or other detergents. The activation of CTA does not need the myristoylated form of the ARF protein and activating region is not located in the N-terminal region of the ARF(Zhang, etal., 1995).

ARF is an effector of pholpholipase D, PLD, too. ARF activates PLD which is an enzyme that cleaves phophatidylcholine (PC) to make phophatidic acid (PA) and choline. PA acts as an effector in physiological processes like DNA synthesis, cell proliferation, and secretory responses. The activation of PLD is GTP-dependent and the domain is located somewhere along the first 73 N-terminal residues although the specific site is unclear(Zhang, etal., 1995).