The guanylate-binding proteins: emerging insights into the biochemical properties and functions of this family of large interferon-induced guanosine triphosphatase

Abstract

Originally identified by their unusual ability to bind guanosine monophosphate (GMP) nucleotide agarose, the guanylate-binding proteins (GBPs) were used extensively to promote our understanding of interferon-induced gene transcription and as markers of interferon responsiveness. Structural and biochemical analyses of human GBP-1 subsequently demonstrated that the GBPs are a unique subfamily of guanosine triphosphatase (GTPases) that hydrolyze guanosine triphosphate (GTP) to both guanosine diphosphate (GDP) and GMP. As members of the larger dynamin superfamily of GTPases, GBPs exhibit such properties as nucleotide-dependent oligomerization and concentration-dependent GTPase activity. Recently, progress has been made in assigning functions to members of the GBP family. While many of these functions involve protection against intracellular pathogens, a growing number of them are not directly related to pathogen protection. It is currently unclear how the unusual properties of GBPs contribute to this growing list of functions. As future studies uncover the molecular mechanism(s) of action of the GBPs, we will gain a greater understanding of how individual GBPs can mediate what currently appears to be a divergent set of functions.

FIG. 1.

Schematic of hGBP-1 structure. The large G domain of hGBP-1 is represented by a ball, and the α-helical regions from helix 6 through 13 are represented by barrels (reprinted from Vestal 2005). The schematic was based on the structural information from the study by Prakash and others (2000a).