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

Abstract

Interferon-γ is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-γ are guanylate-binding proteins such as GBP1 and GBP2 (refs 1, 2). These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity³ and an antiviral effect⁴. Here we have determined the crystal structure of full-length human GBP1 to 1.8 Å resolution. The amino-terminal 278 residues constitute a modified G domain with a number of insertions compared to the canonical Ras structure, and the carboxy-terminal part is an extended helical domain with unique features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity⁵.