Structure and function of the selectin ligand PSGL-1

Cummings, Richard D.

doi:10.1590/s0100-879x1999000500004

Cited by 65 publications

(56 citation statements)

References 47 publications

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“…In contrast, cell surface PSGL-1 efficiently promoted CVA24v binding, suggesting that PSGL-1 glycoproteins contain one or more components that mediate CVA24v binding to target cells. PSGL-1 is a heavily O-glycosylated, mucinlike dimeric glycoprotein that is rich in serine/threonine repeat regions, with no less than 70 potential sites for O-glycosylation and only 3 potential sites for N-glycosylation on each subunit (17,63). The majority of the glycans on PSGL-1 are nonfucosylated, nonsialylated core 2 O-glycans, and thus, only a few of these structures contain sLe X (2,72).…”

Section: Discussionmentioning

confidence: 99%

Coxsackievirus A24 Variant Uses Sialic Acid-Containing O -Linked Glycoconjugates as Cellular Receptors on Human Ocular Cells

Mistry¹,

Inoue²,

Jamshidi³

et al. 2011

J Virol

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Coxsackievirus A24 variant (CVA24v) is a main causative agent of acute hemorrhagic conjunctivitis (AHC), which is a highly contagious eye infection. Previously it has been suggested that CVA24v uses sialic acidcontaining glycoconjugates as attachment receptors on corneal cells, but the nature of these receptors is poorly described. Here, we set out to characterize and identify the cellular components serving as receptors for CVA24v. Binding and infection experiments using corneal cells treated with deglycosylating enzymes or metabolic inhibitors of de novo glycosylation suggested that the receptor(s) used by CVA24v are constituted by sialylated O-linked glycans that are linked to one or more cell surface proteins but not to lipids. CVA24v bound better to mouse L929 cells overexpressing human P-selectin glycoprotein ligand-1 (PSGL-1) than to mocktransfected cells, suggesting that PSGL-1 is a candidate receptor for CVA24v. Finally, binding competition experiments using a library of mono-and oligosaccharides mimicking known PSGL-1 glycans suggested that CVA24v binds to Neu5Ac␣2,3Gal disaccharides (Neu5Ac is N-acetylneuraminic acid). These results provide further insights into the early steps of the CVA24v life cycle.

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Section: Discussionmentioning

confidence: 99%

Coxsackievirus A24 Variant Uses Sialic Acid-Containing O -Linked Glycoconjugates as Cellular Receptors on Human Ocular Cells

Mistry¹,

Inoue²,

Jamshidi³

et al. 2011

J Virol

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“…P-selectin glycoprotein ligand-1 (PSGL-1), a mucin present on the surface of leukocytes, binds P-selectin with high affinity (K d ϭ ϳ300 nM) (43)(44)(45)(46)(47)(48). The interaction is thought to involve two main regions in PSGL-1.…”

Section: Discussionmentioning

confidence: 99%

Selectin Blocking Activity of a Fucosylated Chondroitin Sulfate Glycosaminoglycan from Sea Cucumber

Borsig

Wang

Cavalcante

et al. 2007

Journal of Biological Chemistry

172

105

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Heparin is an excellent inhibitor of P-and L-selectin binding to the carbohydrate determinant, sialyl Lewis x . As a consequence of its anti-selectin activity, heparin attenuates metastasis and inflammation. Here we show that fucosylated chondroitin sulfate (FucCS), a polysaccharide isolated from sea cucumber composed of a chondroitin sulfate backbone substituted at the 3-position of the ␤-D-glucuronic acid residues with 2,4-disulfated ␣-L-fucopyranosyl branches, is a potent inhibitor of P-and L-selectin binding to immobilized sialyl Lewis x and LS180 carcinoma cell attachment to immobilized P-and L-selectins. Inhibition occurs in a concentration-dependent manner. Furthermore, FucCS was 4 -8-fold more potent than heparin in the inhibition of the P-and L-selectin-sialyl Lewis The surface of carcinoma cells exhibits altered glycosylation patterns (1-5), often containing highly branched or sialylated oligosaccharides, especially fucosylated glycans such as sialylLewis X (Sia␣2-3Gal␤1-4(Fuc␣1-3)GlcNAc) and sialyl-Lewis a (Sia␣2-3Gal␤1-3(Fuc␣1-4)GlcNAc). The presence of these oligosaccharides in tumor cells directly correlates with a poor prognosis for cancer patients because of tumor progression and metastatic spread (1-5). The sLe X -oligosaccharides 4 from carcinoma cells act as ligands of the three members of the selectin family of cell adhesion molecules. E-, P-, and L-selectins are vascular receptors for certain normal glycoproteins that contain sialyl-Lewis x,a found on leukocytes and endothelium (6 -8). The selectins also participate in hematogenous metastasis by mediating the interactions of tumor cells with platelets and endothelium (1-3). Hematogenous metastasis occurs through a series of sequential events involving the intravasation of tumor cells into the bloodstream, evasion of innate immune surveillance, adhesion to vascular endothelium of distant organs with subsequent extravasation, and colonization of tissues. It has been proposed that these microemboli of tumor cells with platelets and leukocytes allow tumor cells to evade the immune defenses and eventually colonize distant organs, forming metastatic foci (9 -15). Several studies have shown that a few minutes after intravenous injection, tumor cells are detected in emboli inside pulmonary capillaries in association with platelets and fibrin.Studies from several groups have indicated that tumor metastasis in experimental animals is inhibited by heparin (16 -19). Some clinical studies have also shown a beneficial effect of heparin in some types of human cancer (20 -24). The antimetastatic effect of heparin does not reflect its anticoagulant activity (25, 26) but rather relates to the ability of heparin to inhibit the interaction of sialyl Lewis x,a -rich oligosaccharides on tumor cells with P-selectin on platelets (16,27). In the presence of heparin, tumor cells lose the protection conferred by platelets becoming susceptible to the potentially cytotoxic action of immune effector cells, which leads to the inhibition of metastasis. A single intravascul...

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“…Further post-translational modifications include up to 3 N-linked glycans and sulfation of at least 1 of the 3 tyrosines at the distal end of PSGL-1. 21 PSGL-1 is expressed on most leukocytes, including neutrophils, monocytes, and T lymphocytes, and has been shown to mediate rolling of neutrophils on P-selectin in vitro 20,22 and in vivo. 23 Several chronic and acute diseases, such as stroke, reperfusion/ischemia, transplant rejection, and rheumatoid arthritis, are caused by an excessive recruitment of leukocytes to the site of tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin–mediated neutrophil rolling

Bestebroer

Poppelier

Ulfman

et al. 2006

Blood

166

173

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IntroductionStaphylococcus aureus is a common human pathogen that induces both community-acquired and nosocomial infections. This Grampositive bacterium is well known for its suppurative diseases such as skin-limited abscesses and boils and more seriously endocarditis, sepsis, and toxic shock syndrome. 1,2 Its invasiveness is ascribed to the production of a wide repertoire of cell surface-expressed as well as secreted virulence factors that interfere with host defense. 2,3 Superantigens constitute a large portion of the secreted arsenal of staphylococci and modulate immune responses. They trigger nonspecific activation of T lymphocytes by binding to major histocompatibility complex (MHC) class II molecules on antigenpresenting cells outside the antigen-binding cleft and V ␤ domains of T-cell receptors (TCRs). 4 We have described chemotaxis inhibitory protein of S aureus (CHIPS), an excreted virulence factor of S aureus. 5,6 CHIPS is known to inhibit formylated peptide-and complement factor C5a-induced responses in neutrophils through direct binding to the formyl peptide receptor and C5a receptor (C5aR), respectively. 7 Thereby, CHIPS inhibits the initial activation and migration of neutrophils to the site of infection; thus, it hampers clearance of S aureus by innate immune cells. Recently, the structure of CHIPS consisting of residues 31 to 121 (CHIPS ) was resolved. 8 CHIPS is composed of an ␣-helix packed onto a 4-stranded antiparallel ␤-sheet, a domain also present in the C-terminal domain of superantigens. This protein also revealed to be homologous to the C-terminal domain of staphylococcal superantigen-like 5 (SSL5) and SSL7.SSLs are a family of secreted proteins identified through sequence homology to staphylococcal and streptococcal superantigens. 9 Eleven different SSLs exist that are encoded on staphylococcal pathogenicity island 2 in a conserved order. Staphylococci contain 7 to 11 different SSLs, and their homology varies between 36% and 67%. Allelic variants show 85% to 100% homology. 10,11 Determination of the crystal structures of SSL5 12 and SSL7 13 also revealed their high structural homology to superantigens; the N-terminal oligonucleotide/oligosaccharide-binding fold and the C-terminal ␤-grasp domain characteristic for superantigens are also observed in SSLs. However, residues important for MHC class II and TCR binding of superantigens are not conserved in SSLs, which may explain their inability to display superantigenic activities. 9,10,12 Recently, Langley et al 14 described binding of complement component 5 and immunoglobulin A (IgA) by SSL7, suggesting a role for SSLs in staphylococcal defense against host immune responses. SSL7 was subsequently found to bind the C␣2/C␣3 interface of IgA Fc, which is the adhesion site for the Fc␣RI. 15 So far, no other functions have been linked to the SSLs.Neutrophil recruitment to sites of infection is a multistep process. 16 The initial tethering and rolling of neutrophils on the endothelium of vessel walls during inflammation are mediated by P-selec...

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Structure and function of the selectin ligand PSGL-1

Cited by 65 publications

References 47 publications

Coxsackievirus A24 Variant Uses Sialic Acid-Containing O -Linked Glycoconjugates as Cellular Receptors on Human Ocular Cells

Coxsackievirus A24 Variant Uses Sialic Acid-Containing O -Linked Glycoconjugates as Cellular Receptors on Human Ocular Cells

Selectin Blocking Activity of a Fucosylated Chondroitin Sulfate Glycosaminoglycan from Sea Cucumber

Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin–mediated neutrophil rolling

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