Crystal structures reveal nucleotide-induced conformational changes in G motifs and distal regions in human guanylate-binding protein 2.

ABSTRACT: Guanylate-binding proteins (GBPs) are interferon-inducible GTPases that confer protective immunity against a variety of intracellular pathogens. GBP2 is one of the two highly inducible GBPs, yet the precise mechanisms underlying the activation and regulation of GBP2, in particular the nucleotide-induced conformational changes in GBP2, remain poorly understood. In this study, we elucidate the structural plasticity of GBP2 upon nucleotide binding through crystallographic analysis. By determining the crystal structures of GBP2 G domain (GBP2GD) in complex with GDP and nucleotide-free full-length GBP2 with K51A mutation (GBP2^K51A), we unveil distinct conformational states adopted by the nucleotide-binding pocket and distal regions of the protein. Comparison between the nucleotide-fr

SUBMITTER: Roy S 

PROVIDER: S-EPMC11846989 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature