ABC transporters and the export of capsular polysaccharides from Gram-negative bacteria

Silver, Richard P.; Prior, Kelli; Nsahlai, Christiane J.; Wright, Lori

doi:10.1016/s0923-2508(01)01207-4

Cited by 52 publications

(44 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together, KpsMTED are predicted to form a transenvelope complex (3,4,12,13). KpsMTED functions are not confined to a given CPS repeat-unit structure, and one possible explanation of their broad substrate specificity is the presence of a conserved lipid terminus that may be recognized by the ABC transporter (3,5,14,15). This lipid has been implicated in anchoring CPSs to the outer membrane (16).…”

mentioning

confidence: 99%

Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens

Willis

Stupak

Richards

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

117

View full text Add to dashboard Cite

Bacterial capsules are surface layers made of long-chain polysaccharides. They are anchored to the outer membrane of many Gram-negative bacteria, including pathogens such as Escherichia coli , Neisseria meningitidis , Haemophilus influenzae , and Pasteurella multocida . Capsules protect pathogens from host defenses including complement-mediated killing and phagocytosis and therefore represent a major virulence factor. Capsular polysaccharides are synthesized by enzymes located in the inner (cytoplasmic) membrane and are then translocated to the cell surface. Whereas the enzymes that synthesize the polysaccharides have been studied in detail, the structure and biosynthesis of the anchoring elements have not been definitively resolved. Here we determine the structure of the glycolipid attached to the reducing terminus of the polysialic acid capsular polysaccharides from E. coli K1 and N. meningitidis group B and the heparosan-like capsular polysaccharide from E. coli K5. All possess the same unique glycolipid terminus consisting of a lyso-phosphatidylglycerol moiety with a β-linked poly-(3-deoxy- d - manno -oct-2-ulosonic acid) (poly-Kdo) linker attached to the reducing terminus of the capsular polysaccharide.

show abstract

mentioning

confidence: 99%

Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens

Willis

Stupak

Richards

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

117

View full text Add to dashboard Cite

show abstract

“…The poly-Kdo linker is proposed to be a unifying feature of CPSs synthesized via the ABC transporter-dependent pathway (11). It has long been known that the ABC transporter proteins display no specificity for the CPS repeat unit (1,12,13) and that the conserved reducing terminal glycolipid provides an attractive candidate for an export signal. Although the enzymes and processes involved in biosynthesis of the poly-Kdo linker are unknown, the linker consists of β-linked Kdo, and the donor sugar is likely CMP-β-Kdo (14), so the corresponding glycosyltransferase enzyme(s) are predicted to be retaining Kdo transferases (2).…”

mentioning

confidence: 99%

KpsC and KpsS are retaining 3-deoxy- d - manno -oct-2-ulosonic acid (Kdo) transferases involved in synthesis of bacterial capsules

Willis

Whitfield

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Capsules are bacterial surface structures used by many Gram-negative pathogens to evade the host immune system. They are comprised of long carbohydrate chains, called capsular polysaccharides (CPSs), which possess a lipid at one end. The lipid is connected to the CPS through an unusual linker consisting of five to nine residues of an acidic sugar 3-deoxy- d - manno -oct-2-ulosonic acid (Kdo). This study identifies two conserved proteins from CPS assembly systems, KpsC and KpsS, as the enzymes that synthesize the Kdo linker on the terminal lipid. Synthesis of this terminal glycolipid was reconstituted in vitro using purified enzymes and a synthetic lipid acceptor. The data support a unique model for CPS biosynthesis and identify these enzymes as unique targets for antibacterial therapies.

show abstract

“…Group 2 capsules are synthesized by a heterooligomeric membrane-bound biosynthetic complex on the inner face of the cytoplasmic membrane by the sequential action of glycosyltransferases that elongate the polysaccharide at its non-reducing end (14). Translocation across the inner membrane characteristically requires an ABC-2 (ATP-binding cassette) transporter (3,15,16). Although some group 2 genetic loci encode homologs of Wza (6) and models for export have been proposed (16), little is known regarding their structure function.…”

mentioning

confidence: 99%

“…Translocation across the inner membrane characteristically requires an ABC-2 (ATP-binding cassette) transporter (3,15,16). Although some group 2 genetic loci encode homologs of Wza (6) and models for export have been proposed (16), little is known regarding their structure function. The outer membrane component involved in the translocation of group 2 capsular polysaccharides in E. coli is unknown.…”

mentioning

confidence: 99%

Three-dimensional Structure of Wza, the Protein Required for Translocation of Group 1 Capsular Polysaccharide across the Outer Membrane of Escherichia coli

Beis

Collins

Ford

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Wza is a highly conserved multimeric outer membrane protein complex required for the surface expression of the serotype K30 group 1 capsular polysaccharide in Escherichia coli. Here we present the first three-dimensional structure of this type of polysaccharide exporter at a 15.5-Å resolution obtained using single particle averaging on a dataset of cryo-negatively stained protein.Previous structural studies on purified Wza have revealed a homo-oligomeric ring structure that is most probably composed of eight subunits. Symmetry analysis of the three-dimensional structure combined with biochemical two-and three-dimensional crystallographic data strongly suggest that Wza is an octameric complex with a C4 quasi-rotational symmetry and is organized as a tetramer of dimeric subunits. Wza is best described as a stack of two 4-Å high rings with differing diameters providing a mushroom-like aspect from the side. The larger ring has a distinctive square shape with a diameter of 115 Å, whereas the smaller is almost circular with a diameter of 90 Å. In the center of the complex and enclosed by the four symmetrical arms is a small elliptical cagelike cavity of ϳ40 Å in diameter. The central cavity is effectively sealed at the top and bottom of the complex but has small inter-arm holes when viewed from the side. We discuss the structure of this complex and implications in the surface translocation of cell-surface polysaccharide.

show abstract

ABC transporters and the export of capsular polysaccharides from Gram-negative bacteria

Cited by 52 publications

References 26 publications

Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens

Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens

KpsC and KpsS are retaining 3-deoxy- d - manno -oct-2-ulosonic acid (Kdo) transferases involved in synthesis of bacterial capsules

Three-dimensional Structure of Wza, the Protein Required for Translocation of Group 1 Capsular Polysaccharide across the Outer Membrane of Escherichia coli

Contact Info

Product

Resources

About