STRUCTURE OF THE SEC7 DOMAIN OF THE ARF EXCHANGE FACTOR ARNO

Small G proteins switch from a resting, GDP-bound state to an active, GTP-bound state. As spontaneous GDP release is slow, guanine-nucleotid e-exchange factors (GEFs) are required to promote fast activation of s mall G proteins through replacement of GDP with GTP in vivo(1). Famili es of GEFs with no sequence similarity to other GEF families have now been assigned to most families of small G proteins. In the case of the small G protein Arf1, the exchange of bound GDP for GTP promotes the coating of secretory vesicles in Golgi traffic(2). An exchange factor for human Arf1, ARNO(3), and two closely related proteins, named cytoh esin 1 (ref. 4) and GPS1 (ref. 5), have been identified. These three p roteins are modular proteins with an amino-terminal coiled-coil, a Cen tral Sec7-like domain and a carboxy-terminal pleckstrin homolog domain . The Sec7 domain contains the exchange-factor activity(3). It was fir st found in Sec7, a yeast protein and is present in several other prot eins, including the yeast exchange factors for Arf, Gea1 and Gea2 (ref s 7-9). Here we report the crystal structure of the Sec7 domain of hum an ARNO at 2 Angstrom resolution and the identification of the site of interaction of ARNO with Arf.