membrane localization domain (MLD) of BteA (Bordetella T3SS effector A) cytotoxin, the N-terminal domain of Photox toxin and related proteins
This family includes the MLD located in the N-terminal minimal membrane-binding segment of BteA (residues 1-131, BteA131), which has also been referred to as the lipid raft targeting (LRT) domain/motif. BteA is a type III secretion system (T3SS) effector protein from Bordetella pertussis, a bacterial respiratory pathogen and the causative agent of whooping cough. The BteA131 segment is multifunctional: in addition to targeting phosphatidylinositol (PI)-rich microdomains in the host membrane, it binds its cognate chaperone BtcA. The MLD adopts a four-helix bundle structure, with a positively charged surface that targets phosphatidylinositol 4,5-bisphosphate (PIP2) in the host membrane via critical arginine and lysine residues. A flexible region preceding the BteA helical bundle contains the characteristic beta-motif required for binding BtcA. This domain has significant sequence similarity to the N-terminal domain of effectors and the endo-domain of RTX-type toxins from Photorhabdus luminescens. This family includes the N-terminal domain of Photorhabdus laumondii Photox toxin; little is known about the N-terminus of Photox, but its C-terminus is an actin-targeting ADP-ribosyltransferase.
Comment:these residues may facilitate membrane interactions; based on a mutagenesis investigation of the PIP2 binding site of BteA using structural and biophysical methods including NMR and Small-angle X-ray scattering (SAXS)
Comment:for BteA131, a positively charged surface, including these critical K and R residues, targets PIP2 in the host membrane; BteA appears to rely on a 'side-on' interaction mode