ADP-ribosylation Factors: ARF Structure and Function

腺苷二磷酸核醣基化因子：ARF之構造與功能

蔡素蟾(Su-Chen Tsai) ； Ronald Adamik ； Joel Moss ； Martha Vaughan

《Zoological Studies》 34卷1期 (1995/01) Pp. 1-9

摘要

腺苷二磷酸核醣基化因子（ARFs）係分子量約20KDa的鳥嘌呤核苷酸結合蛋白。最初由於其具有活化霍亂毒素腺苷二磷酸核醣基化轉移酶的能力而被發現，爾後發現此因子亦存在於高爾基體，並參與其真核細胞囊胞的運送。從賈弟蟲（Giardia）到哺乳類，ARFs具有高度穩定性。依胺基酸序列、分子大小及基因構造，哺乳類和果蠅的ARFs可分為三類。ARFs需要GTP（鳥糞嘌呤核苷三磷酸鹽）或類似物以活化霍亂毒素，而磷脂與清潔劑可促進其作用。霍亂毒素之活化與ARFs的N-端十三個胺基酸無關，然而ARFs之N端十四烷酸化可增強ARFs與高爾基體和其它膜之結合。GTP和形成的水溶性複合體可能會促進ARFs與膜之結合。水溶性複合體的形成過程被brefeldin A（BFA）所抑制，此BFA是一種會破壞高爾基體的真菌代謝物。水溶性複合體中有一種成分即與磷脂有關的鳥嘌呤核苷酸交換蛋白質。此種經純化的蛋白質與BFA無關，但可促進ARFs與GTP的結合，進而與高爾基體結合，最後和Coatomer蛋白結合引起囊胞發芽。最近研究結果顯示ARFs可活化磷脂酶D（phospholipase D），其藉由磷脂酸鹽（Phosphatidate）與其代謝物的產生，可能和ARFs敢抬膜（囊胞）之運送功能有關。

關鍵字

霍亂毒素 ； 腺苷二磷酸核醣基化因子 ； 鳥嘌呤核苷酸結合蛋白 ； 磷脂酶D

並列摘要

ADP-ribosylation factors (ARFs) are - 20-kDa guanine nucleotide-binding proteins initially discovered by their ability to activate cholera toxin ADP-ribosyltransferase activity. Subsequently they were shown to be present in the Golgi and to participate in vesicular trafficking in eukaryotic cells. ARFs are highly conserved from Giardia to mammals. Mammalian and Drosophila ARFs fall into three classes based on size, amino acid sequence, and gene structure. The ability of ARFs to activate cholera toxin requires GTP or an analogue and is promoted by phospholipids and detergents. Toxin activation is independent of the amino terminal thirteen amino acids. However, myristoylation at the amino terminus promotes association of ARFs with Golgi and other membranes. Binding to membranes appears to be enhanced by GTP and a soluble complex in a process inhibited by brefeldin A (BFA), a fungal metabolite known to disrupt Golgi. One component of the soluble complex is a phospholipid-dependent guanine nucleotide-exchange protein, which, in a purified state, is independent of BFA and enhances ARF binding of GTP. Activation of ARF by GTP binding promotes its association with Golgi and the subsequent binding of the coatomer proteins, which initiate the vesicular budding process. ARFs have recently been shown to activate phospholipase D which, through the generation of phosphatidate and its metabolites, may be responsible for some of the ARF-initiated membrane trafficking events.

並列關鍵字

Cholera toxin ； ADP-ribosylation factors ； Guanine nucleotide-binding proteins ； Brefeldin A ； Phospholipase D