Summary: Complex glycoconjugates play critical roles in the biology of microorganisms. which serve as chain termination and/or export signals and by the presence (or absence) of a discrete substrate-binding domain name in the nucleotide-binding domain name polypeptide of the ABC transporter. A bioinformatic survey examining ABC exporters from known oligo- and polysaccharide biosynthesis loci identifies conserved nucleotide-binding domain name protein families that correlate well with themes in the structures and assembly of glycans. The familial relationships among the ABC exporters generate hypotheses concerning the biosynthesis of structurally diverse oligo- and polysaccharides which play important roles in the biology of bacteria with different lifestyles. INTRODUCTION In prokaryotes glycosylated macromolecules (glycoconjugates) often form the point of first contact between the organism and its immediate environment. Surface glycoconjugates play major roles in the maintenance of cell envelope structure protection against host immune defenses signaling events and the formation of biofilms. The structures of bacterial glycans show tremendous diversity in terms of component sugars noncarbohydrate modifications and linkage configurations. They are also attached to a broad range of molecules including lipids peptidoglycan and proteins. Despite the remarkable diversity Roxadustat in oligo- and polysaccharide structures and the manners in which they are presented around the cell surface the number of fundamentally different pathways used in polysaccharide synthesis and export across the inner membrane is usually relatively limited. For polysaccharides or oligosaccharides synthesized directly from activated precursors consisting of nucleotide mono- or diphosphoglycoses there are currently just three known export strategies that have been described in any detail (Fig. ?(Fig.1);1); these have been termed “Wzx/Wzy FANCD dependent ” “ATP-binding cassette (ABC) transporter dependent ” and “synthase dependent ” based on characteristic components. These three general assembly-export strategies are not confined to the assembly of any one class of glycoconjugate. It is the actions that occur beyond synthesis and export (i.e. attachment of the glycan to a final acceptor molecule) that define the type of glycoconjugate that is formed. Most of our current understanding of these systems has been obtained in the context of lipopolysaccharide (LPS) O-antigen Roxadustat polysaccharide (O-PS) and capsular or exopolysaccharide (CPS or EPS) assembly and these have been reviewed elsewhere (121 173 FIG. 1. Models for processes involved in the synthesis and (79) and (109 143 In the absence of the ABC transporter polymer is usually synthesized by each of these systems but it never leaves the cytoplasm. Later a similar phenomenon was recognized in the biosynthesis of LPS O-PS in O:3 (182). Subsequently ABC transporters were identified in the assembly of teichoic acid in 168 (83) and in the protein glycosylation system from (2). ABC transporters are now known to be involved in the export of representatives from all of the major classes of cell surface glycoconjugates. By mining genomic information to examine the distribution of “glyco-focused” ABC transporters it is clear that they play pivotal roles in the glycobiology of many bacteria even though there are many cases where the exact nature and structure of the Roxadustat export substrate have not been established. Roxadustat In each of these systems the organism must overcome the same challenges. First the export system must engage a biosynthesis pathway often involving multiple proteins with different catalytic activities. Second the exporter must handle a large hydrophilic (and sometimes charged) substrate often attached to a hydrophobic lipid acceptor. Here we describe our current understanding of the structure and function of glycan ABC transporters and illustrate how bioinformatic analyses can extend this knowledge to other cell surface glycoconjugates. STRUCTURE AND FUNCTION OF ABC TRANSPORTERS ABC transporters represent a massive protein superfamily and play diverse roles in biological processes which span the biological kingdoms. In bacteria ABC transporters are involved in the uptake of nutrients (e.g. some sugars amino acids and vitamins). They also participate in the export of molecules with remarkable structural diversity including various drugs and other small-molecule inhibitors proteins lipids and (in the context of this.