Structure of YbbAP-TesA: a Type VII ABC transporter lipid-hydrolase complex

Type VII ABC transporters are ATP-powered membrane protein complexes that drive key biological processes in the bacterial cell envelope. In E. coli, three of the four Type VII ABC systems have been extensively characterised including: the FtsEX-EnvC cell division complex, the LolCDE-LolA lipoprotein trafficking machinery and the MacAB-TolC efflux pump. Here we describe a fourth E. coli Type VII ABC system, YbbAP-TesA, which combines a Type VII ABC transporter with a multifunctional hydrolytic enzyme. Structures of the complete YbbAP-TesA complex, and of YbbAP with and without bound ATP analogues, capture the long-range transmembrane conformational changes that are the hallmark of this ABC superfamilys mechanotransmission mechanism. We further show that YbbAP-TesA can hydrolyse a variety of ester and thioester substrates and experimentally confirm a constellation of active site residues in TesA. Our data suggests YbbAP has a role in extracting hydrophobic molecules from the inner membrane and presenting these to TesA for hydrolysis. The work extends collective knowledge of the remarkable diversity of the ABC superfamily and establishes a new function for Type VII ABC transporters in bacterial cells. Significance StatementType VII ABC transporters are unique to bacteria and play important roles in bacterial physiology including cell division, antibiotic resistance, siderophore secretion, antibiotic sensing, toxin secretion, biofilm regulation and lipoprotein trafficking. Here we identify a complex that combines an atypical Type VII ABC transporter (YbbAP) with a periplasmic lipid hydrolase (TesA). The YbbAP-TesA complex is structurally and functionally distinct from all known Type VII ABC transporter systems including FtsEX-EnvC, LolCDE-LolA, BceAB-BceS and MacAB-TolC. Structures suggest that YbbAP-TesA uses ATP-driven mechanotransmission to extract substrates from the inner membrane and hydrolyse them in the periplasmic space. The discovery and characterisation of YbbAP-TesA highlights the structural and functional diversity of Type VII ABC transporter complexes and suggests a new function for these proteins in the bacterial cell envelope.