Helical Domain Changes between hGBP3 and hGBP3ΔC Result in Distinct Oligomers and Anti-HCV Activity.

Human guanylate binding proteins (hGBPs), which are large GTPases, are crucial for cell-autonomous immunity, including antiviral activity. hGBPs contain two domains: an N-terminal catalytic domain and a C-terminal helical domain. hGBP3 and its splice variant hGBP3ΔC have been shown to possess anti-influenza activity in lung epithelial cells.

Helical domain of hGBP3 cannot stimulate the second phosphate cleavage of GTP.

Interferon-gamma-inducible large GTPases, hGBPs, possess antipathogenic and antitumor activities in human cells. Like hGBP1, its closest homolog, hGBP3 has two domains; an N-terminal catalytic domain and a C-terminal helical domain, connected by an intermediate region. The biochemical function of this protein and the role of its domains in substrate hydrolysis have not yet been investigated.

Stimulation of GMP formation in hGBP1 is mediated by W79 and its effect on the antiviral activity.

Interferon-inducible large GTPases are critical for innate immunity. The distinctive feature of a large GTPase, human guanylate binding protein-1 (hGBP1), is the sequential hydrolysis of GTP into GMP via GDP. Despite several structural and biochemical studies, the underlying mechanism of assembly-stimulated GMP formation by hGBP1 and its role in immunity are not fully clarified.