Phospholipid binding residues of eukaryotic membrane-remodelling F-BAR domain proteins are conserved in Helicobacter pylori CagA.

backgroundCytotoxin associated gene product A (CagA) is an oncogenic protein secreted by the gastric bacterium Helicobacter pylori. Internalization of CagA by human epithelial cells occurs by an unknown mechanism that requires interaction with the host membrane lipid phosphatidylserine.

findingsLocal homology at the level of amino acid sequence and secondary structure has been identified between the membrane-tethering region of CagA and the lipid-binding Fes-CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domains of eukaryotic proteins. The F-BAR proteins are major components of the endocytic machinery. In addition to the membrane-binding F-BAR domains, they contain other domains that interact with actin-regulatory networks and mediate interplay between membrane dynamics and cytoskeleton re-arrangements. Positively charged residues found on the lipid binding face of the F-BAR domains are conserved in CagA and represent residues involved in CagA binding to lipids.

conclusionsThe homologies with F-BAR proteins extend to lipid binding specificities and involvement in reorganization of the actin cytoskeleton. CagA and F-BAR domains share binding specificity for phosphatidylserine and phosphoinositides. Similar to the F-BAR proteins, CagA has a membrane-binding module and a module that shares structural homology with actin-binding proteins, and, like eukaryotic F-BAR domain proteins, CagA function is linked to actin dynamics. The uncovered similarities between the bacterial effector protein and eukaryotic F-BAR proteins suggest convergent evolution of CagA towards a similar function.