3.A.1.112.9
ABC bacteriocin exporter with two peptidase domains, Pcat1. 3-D structures are known (4S0F, 6V9Z, 4RY2). The pathway for peptide export consists of an large α-helical barrel for small folded peptides.  ATP binding alternates access to the transmembrane pathway and reglates protease activity (Lin et al. 2015). Subunit asymmetry of the M3-M4 loops contribute to optimizing AChR activation through allosteric links to the channel and the agonist binding site (Shen et al. 2005). Structures were more recently determined in the absence and presence of ATP, revealing how ATP binding regulates the protease activity and access to the translocation pathway. Two substrate CtAs, 90-residue polypeptides, are bound via their N-terminal leader peptides, but only one is positioned for cleavage and translocation. The structures were determined in the absence and presence of ATP, revealing how ATP binding regulates the protease activity and access to the translocation pathway. It seems that substrate cleavage, ATP hydrolysis, and substrate translocation are coordinated in a transport cycle (Kieuvongngam et al. 2020). The N-terminal C39 peptidase (PEP) domain of PCAT1 processes its natural substrate, CtA, by cleaving a conserved -GG- motif to separate the cargo from the leader peptide prior to secretion. The ATP-mediated association between PEP and the transmembrane domains of PCAT1 offers a putative mechanism to optimize peptide cleavage by regulating the width and flexibility of the enzyme active site (Bhattacharya and Palillo 2021). Structures of the peptidase-containing ABC transporter PCAT1 under equilibrium and nonequilibrium conditions have been solved (Kieuvongngam and Chen 2022).