Cryo-EM analysis of the atypical chemokine receptor ACKR1 in complex with Staphylococcus aureus pore forming toxin component HlgA

The aim of this research is to solve a first high-resolution structure of a G protein-coupled receptor (GPCR) in complex with a Staphylococcus aureus (SA) pore forming toxin component, namely γ hemolysin A (HlgA). We have obtained complexes of monomeric HlgA and atypical chemokine receptor 1 (ACKR1), which represent the initial molecular step leading to the formation of transmembrane pores that are able to lyse human red blood cells (which express ACKR1). This work will provide a structural basis to understand how pathogenic SA bacteria hijack human GPCRs, and help design potential inhibitors or anti-SA vaccines.