Structural and functional significance of <i>Aedes aegypti</i> AgBR1 flavivirus immunomodulator.

ABSTRACT: Zika virus (ZIKV), an arbovirus, relies on mosquitoes as vectors for its transmission. During blood feeding, mosquitoes inoculate saliva containing various proteins. Recently, AgBR1, an Aedes aegypti salivary gland protein, has gained attention for its immunomodulatory potential, along with another protein, called NeSt1. We have determined the crystal structure of AgBR1 at 1.2 Å resolution. Despite its chitinase-like fold, we demonstrated that AgBR1 does not bind to chitobiose or chitinhexaose, while a key mutation in the catalytic site abrogates enzymatic activity, suggesting that the protein's function has been repurposed. Our study also shows that AgBR1 and NeSt1, when presented to murine primary macrophages, alter cellular pathways related to virus entry by endocytosis, immune r

SUBMITTER: Martinez-Castillo A 

PROVIDER: S-EPMC12090808 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature