Structure of human guanylate-binding protein 1 representing a unique classof GTP-binding proteins

Interferon-gamma is an immunomodulatory substance that induces the expressi on of many genes to orchestrate a cellular response and establish the antiv iral state of the cell. Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2 (r efs 1, 2). These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity(3) and an antiviral effect(4). Here we have determined the crystal structure of full-length human GBP1 to 1.8 Angstrom resolution. The amino-terminal 278 residues constitute a modif ied G domain with a number of insertions compared to the canonical pas stru cture, and the carboxy-terminal part is an extended helical domain with uni que features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that inc ludes Mx and dynamin, the common property of which is the ability to underg o oligomerization with a high concentration-dependent GTPase activity(5).