Trends in Biochemical Sciences
Protein Sequence MotifThe PA14 domain, a conserved all-β domain in bacterial toxins, enzymes, adhesins and signaling molecules
Section snippets
Domain definition
PSI–BLAST search of the NCBI non-redundant protein database (http://www.ncbi.nlm.nih.gov) using the insertion sequence of the A. tumefaciens β-glucosidase (residues 361–560 of SWISS-PROT P27034) as the query and inclusion E-value of 0.001 converged after nine iterations retrieving 132 proteins (Figure 1), including a Bacteroides thetaiotaomicron genomic [12] sequence BT2948 protein (GenBank accession AAO78054), which contains an insertion of the same domain (hereafter referred to as PA14
Domain architectures
Comparisons of the retrieved sequences against Pfam [6], SMART [18] and CDD [19] domain databases revealed many diverse domain combinations involving the PA14 domain (Figure 2). Most of the experimentally characterized PA14-containing proteins are involved in carbohydrate binding and/or metabolism (Figure 2), including glycoside hydrolase domains of families 2, 3, 10, 20 and 31 in the classification of Coutinho and Henrissat (http://afmb.cnrs-mrs.fr/~cazy/CAZY/index.html) and the recently
Domain function
Taken together, several lines of evidence suggest that the PA14 domain could be a novel carbohydrate-binding module:
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The PA14 domain is combined in a mosaic manner with various catalytic or non-catalytic domains directly or indirectly implicated in binding carbohydrate or peptidoglycan.
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For the yeast flocculins, carbohydrate binding has been demonstrated for a region overlapping the PA14 domain [21].
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The notion that the PA14 β-sandwich domain might have a carbohydrate-binding function is also
Future perspectives
The hypothesis that the PA14 domain binds carbohydrates raises interesting possibilities about its participation in anthrax toxin activation. Simple hydrolysis of the PA20–PA63 bond in intact PA is insufficient in itself to give subunit separation [14], which raises the question of what drives separation of the PA20 and PA63 in vivo. Attachment of the PA14 domain of the PA20 fragment to an extracellular matrix component could provide an explanation for this apparent inconsistency and offer an
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RTX Adhesins are Key Bacterial Surface Megaproteins in the Formation of Biofilms
2019, Trends in MicrobiologyCitation Excerpt :Many RTX adhesins contain the PA14 sugar-binding domain, which might target cells to extracellular polysaccharides in biofilms, to carbohydrate substrates, or to surface glycolipids or glycoproteins on various cell types (Figure 1). Originally discovered as a domain of unknown function in the protective antigen (PA) toxin from Bacillus anthracis, the domain has been found in proteins from many different organisms, ranging from bacteria and yeast, to more complex eukaryotes like humans [23,24]. The involvement of PA14 in microorganism adhesion has been well documented in the yeasts Saccharomyces cerevisiae and Candida glabrata, where its sugar-binding function is used for self-adherence (flocculation) and human cell adhesion, respectively [25–27].
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2017, Journal of ProteomicsCitation Excerpt :These four CBM-containing proteins are all predicted to be secreted, and all but Cpin_5674 are processed via the T9SS pathway [39]. Additionally, a protein not detected in the glucose samples was Cpin_2448, which contains a CBM13 as part of a multi-modular protein with a conserved domain of unknown function (DUF), two PA14 domains [46] and a beta/gamma crystallin domain. The structures of the two polysaccharides studied here necessitate different degradative approaches.
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2016, Current Opinion in Structural BiologyCitation Excerpt :Notably, PA14 domains do not function unconditionally to aid carbohydrate binding in all GH families, but can in fact sterically block longer oligosaccharides in other contexts [36•]. Thus, extreme caution warranted in assigning function for these and other non-catalytic domains based on bioinformatics in the absence of experimental data [16••,35]. The three-dimensional structure of CjBgl35, which is capable of hydrolyzing β(1→2)-galactosyl units from either canonical position in dicot fucogalacto-XyG (Figure 1), similarly revealed a molecular architecture specifically adapted for XyG saccharification.