The PA14 domain, a conserved all-β domain in bacterial toxins, enzymes, adhesins and signaling molecules

Abstract

Iterative database searches starting from a domain insert sequence in bacterial β-glucosidases reveals the presence of a conserved domain shared by a wide variety of bacterial and eukaryotic proteins. These include other glycosidases, glycosyltransferases, proteases, amidases, adhesins, and bacterial toxins such as anthrax protective antigen (PA). The domain also occurs in the mammalian protein fibrocystin, mutation of which leads to autosomal-recessive polycystic kidney and hepatic disease. The crystal structure of PA shows that this domain (named PA14 after its location in the PA 20 pro-peptide) has a β-barrel architecture. A PA14 sequence alignment suggests a binding function, rather than a catalytic role, whereas the PA14 domain distribution is compatible with carbohydrate binding.