Periplasmic adaptor proteins are components of bacterial three-component membrane efflux pumps, which are essential for expelling antibiotics, metals and other toxic compounds from bacteria. They are usually multi-domain proteins, in which the domains are arranged in a linear manner: a membrane proximal domain, a beta-barrel domain, a lipoyl domain and an alpha-helical domain.

This superfamily comprises the beta barrel domain and it is found in bacterial drug and metal resistance nodulation cell division (RND)-driven efflux pumps adaptor proteins, such as MexA (from MexAB-OprM efflux pump in Pseudomonas aeruginosa), BesA (from the spirochete Borrelia burgdorferi), CusA (from the CusCBA efflux system), ZneB (the membrane fusion protein component of the ZneCAB efflux complex), MacA (from MacAB-TolC pump), EmrA or AcrA (in E. coli, EmrAB-TolC and AcrA-AcrB-TolC). Structurally, this domain is a beta barrel composed of six to eight beta-strands, and it may contain an alpha-helix situated at entrance to the barrel. It has been suggested that this domain plays a role in binding efflux substrates.

Pfam clan [PfamClan:CL0105],PMID:15117957,PMID:23851070,PMID:23499019,PMID:15226509,PMID:21350490,PMID:20534468,PMID:19254725,PMID:24996185,PMID:22308040