Characterization of human guanylate binding protein 3

Krittika Roy, Qian Yin

Florida State University

Human Guanylate Binding Protein 3 (hGBP3) has emerged as a key player in immune modulation and cancer biology, especially in glioblastoma multiforme (GBM), the most aggressive type of brain cancer. hGBP3 regulates the SQSTM1-ERK1/2 signaling cascade, making it a promising therapeutic target in GBM treatment. Furthermore, a splice form of human GBP3 exhibits robust antiviral activity against influenza, validating and expanding our understanding of GBP-mediated immune responses. Despite the crucial role hGBP3 plays in inflammatory responses, the precise mechanisms governing GBP3 activation and regulation have received little attention. Our research intends to illuminate the biochemical and structural characteristics of hGBP3. We have observed hGBP3 shows distinct solution behavior, atypical to most hGBPs. Despite its significant sequence similarity to other homologs such as hGBP1 and hGBP2, hGBP3 has low enzymatic efficiency. Our research aims to unravel the structural alterations behind this disparate behavior in solution state, as well as the reduction in hydrolytic activity of this protein. Thus, our investigation might be able to precisely reveal how these alterations explain hGBP3's functional uniqueness within this GTPase family. Further investigation into hGBP3's molecular mechanisms and better understanding of its structural biology hold potential for novel targeted therapeutic approaches in cancer and inflammatory disorders.