Figure 9.

Arf · GTP loss model for the effect of BFA on GBF1 association with membranes. GBF1 and Arf · GDP are recruited to specific membranes through interaction with distinct receptors. BFA absent (top), in the presence of a regulatory Arf · GTP (blue), membrane-bound GBF1 acquires an active conformation that can interact with membrane-bound substrate Arf · GDP (red) and promote release of GDP. GTP loading causes the release of a new Arf · GTP (red) and frees up active GBF1 for another cycle of nucleotide exchange. GBF1 dissociates rapidly from its receptor under these conditions but can activate multiple Arf substrates per binding cycle. BFA present (bottom), BFA forms an abortive complex Arf · GDP · BFA · GBF1 complex with membrane-bound GBF1 and blocks nucleotide exchange. Arf-GAP activity leads to rapid loss of regulatory Arf · GTP from the membrane, which induces a conformational change in GBF1. In absence of Arf · GTP, membrane-bound GBF1 interacts poorly with Arf · GDP and dissociates slowly from its receptor. Some Arf · GDP remain associated with their receptors.