ADP-ribosylation factor 1–Sec7 domain protein–protein interface (ARF1–Sec7d PPI)

The ARF1–Sec7 domain protein–protein interface is a critical regulatory site for the activation of ADP-ribosylation factor 1 (ARF1), a small GTPase that orchestrates vesicular trafficking and Golgi apparatus maintenance. Activation occurs when a Sec7 domain-containing guanine nucleotide exchange factor (GEF) binds to ARF1–GDP, facilitating the release of GDP and the binding of GTP. This specific interface is a well-validated pharmacological target, most notably by the natural product Brefeldin A, which traps the complex in an 'abortive' intermediate state. By stabilizing this inactive complex, inhibitors prevent the recruitment of coat proteins required for vesicle budding, leading to the collapse of the Golgi stack and inhibition of the secretory pathway. This mechanism has therapeutic potential in oncology, where ARF1 signaling is often upregulated to support rapid growth and metastasis, and in infectious diseases, as many viruses and bacteria hijack this pathway for cellular entry and replication.

Other names

ARF1–Sec7 domain interfaceARF1–GEF interfaceARF1–GDP/Sec7d complexSec7 domain-containing ARF guanine nucleotide exchange factor interface

Stabilization of the abortive ARF1–GDP–Sec7 domain complex to prevent the exchange of GDP for GTP, thereby inhibiting ARF1 activation and subsequent vesicle formation.