The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide

Foxall, Carrol; Watson, J. R.; Dowbenko, Donald; Fennie, Christopher; La, Lasky; Kiso, Makoto; Hasegawa, Akira; Asa, Darwin; Brandley, Brian K.

doi:10.1083/jcb.117.4.895

Cited by 672 publications

(380 citation statements)

References 44 publications

Supporting

Mentioning

370

Contrasting

Unclassified

Order By: Relevance

“…E-selectin is expressed on the endothelium within 2 h of stimulation, and it adheres to sialylated Lewis X sugars of leukocyte surface glycoproteins (29,50,58 and p2-integrins on leukocytes is facilitated after selectin interactions. Pj-integrin-ICAM-l adhesion appears to be critical for migration of leukocytes into tbe junctions between the endothelial cells and, ultimately, to the abluminal surface of the blood vessels.…”

Section: General Features Of Am Role In Allergic Inflammationmentioning

confidence: 99%

Adhesion molecules of allergic inflammation: recent insights into their functional roles

Canonica

Ciprandi

Buscaglia

et al. 1994

Allergy

View full text Add to dashboard Cite

show abstract

Section: General Features Of Am Role In Allergic Inflammationmentioning

confidence: 99%

Adhesion molecules of allergic inflammation: recent insights into their functional roles

Canonica

Ciprandi

Buscaglia

et al. 1994

Allergy

View full text Add to dashboard Cite

show abstract

“…Both the observed secondary isotope effect and the inhibition by GDP-2F-Fuc are consistent with a charged, sp 2 -hybridized, transition-state structure. A convenient and efficient synthesis of GDP-[1-2 H]-Fuc and GDP-2F-Fuc and a nonradioactive, fluorescence assay for fucosyltransferase activity have been developed.The R-1,3-fucosylated oligosaccharide structures are central to numerous cell-cell interactions (Ichikawa et al, 1994) such as inflammation, tumor development, and blood clotting (Foxall et al, 1992;Parekh & Edge, 1994). Five distinct human R-1,3-fucosyltransferases have been cloned (KukowskaLatallo et al, 1990;Lowe et al, 1991;McCurley et al, 1995;Reguigne-Arnould et al, 1995;Sasaki et al, 1994; Weston et al, 1992a,b) and shown to have different acceptor sugar specificity.…”

mentioning

confidence: 99%

Mechanism of Human α-1,3-Fucosyltransferase V: Glycosidic Cleavage Occurs Prior to Nucleophilic Attack

et al. 1997

View full text Add to dashboard Cite

R-1,3-Fucosyltransferase V (FucT V) catalyzes the transfer of l-fucose from the donor sugar guanosine 5′-diphospho--l-fucose (GDP-Fuc) to an acceptor sugar. A secondary isotope effect on the fucosyltransfer reaction with guanosine 5′-diphospho-[1-2 H]--l-fucose (GDP-[1-2 H]-Fuc) as the substrate was observed and determined to be D V ) 1.32 ( 0.13 and D V/K ) 1.27 ( 0.07. Competitive inhibition of FucT V by guanosine 5′-diphospho-2-deoxy-2-fluoro--l-fucose (GDP-2F-Fuc) was observed with an inhibition constant of 4.2 µM which represents the most potent inhibitor of this enzyme to date. Incubation of GDP-2F-Fuc with FucT V and an acceptor molecule prior to the addition of GDP-Fuc had no effect on the potency of inhibition, indicating that GDP-2F-Fuc is neither an inactivator nor a slow substrate. Both the observed secondary isotope effect and the inhibition by GDP-2F-Fuc are consistent with a charged, sp 2 -hybridized, transition-state structure. A convenient and efficient synthesis of GDP-[1-2 H]-Fuc and GDP-2F-Fuc and a nonradioactive, fluorescence assay for fucosyltransferase activity have been developed.The R-1,3-fucosylated oligosaccharide structures are central to numerous cell-cell interactions (Ichikawa et al., 1994) such as inflammation, tumor development, and blood clotting (Foxall et al., 1992;Parekh & Edge, 1994). Five distinct human R-1,3-fucosyltransferases have been cloned (KukowskaLatallo et al., 1990;Lowe et al., 1991;McCurley et al., 1995;Reguigne-Arnould et al., 1995;Sasaki et al., 1994; Weston et al., 1992a,b) and shown to have different acceptor sugar specificity. R-1,3-Fucosyltransferase V (FucT V) 1 is responsible for the terminal step in the biosynthesis of Lewis x (Le x ) and sialyl Lewis x (sLe x ) (Figure 1), a tetrasaccharide ligand involved in inflammatory cell adhesion and metastasis (Lasky, 1992;Muramatsu, 1993). Thus inhibition of this enzyme may impede inflammation or cancer progression, and understanding the mechanism of FucT V may lead to the development of effective inhibitors.The R-1,3-fucosyltransferase V-catalyzed reaction proceeds with inversion of configuration at the anomeric center of l-fucose (Weston et al., 1992a). Product inhibition studies have been used to establish that FucT V has an ordered, sequential, bi-bi mechanism with guanosine 5′-diphospho--l-fucose (GDP-Fuc) binding first and the product GDP releasing last (Qiao et al., 1996). FucT V has been shown to have a catalytic residue with pK a ) 4.1, presumably an active-site carboxylate residue . A solvent isotope effect was observed (D V ) 2.9, D V/K ) 2.1) and exploited in a proton inventory study to show that there is a one-proton transfer in the transition state . The transition-state structure of glycosyltransferasecatalyzed reactions has been proposed to have a flattened half-chair conformation with substantial oxocarbenium ion character at the anomeric position (Kim et al., 1988;Murray et al., 1996), analogous to that of the glycosidase reactions (Look et al., 1993;Sinnott, 1990). Consistent with...

show abstract

“…Furthermore, the application of a small force has been paradoxically reported to lengthen the lifetime of selectinligand bonds, whereas force beyond a threshold shortens the lifetime of selectin-ligand bonds 15-17 . Selectins contain an N-terminal calcium-dependent lectin domain, an epidermal growth factor (EGF)-like domain, a variable number of short consensus repeats (SCRs), and transmembrane and cytoplasmic domains 6,18-20 . Selectin ligands consist mainly of mucin-like sialoglycoproteins such as P-selectin glycoprotein ligand 1 (PSGL-1), and all three selectin molecules bind the tetrasaccharide sialyl Lewis X (sLe X ) 21,22 . The crystal structures of the lectin and EGF-like domains of human P-selectin, both bound and unbound to its high-affinity ligand PSGL-1 sulfoglycopeptide, SGP-3, have shown two distinct conformations of Pselectin.…”

mentioning

confidence: 99%

Remodeling of the lectin–EGF-like domain interface in P- and L-selectin increases adhesiveness and shear resistance under hydrodynamic force

2006

View full text Add to dashboard Cite

Crystal structures of the lectin and epidermal growth factor (EGF)-like domains of P-selectin show 'bent' and 'extended' conformations. An extended conformation would be 'favored' by forces exerted on a selectin bound at one end to a ligand and at the other end to a cell experiencing hydrodynamic drag forces. To determine whether the extended conformation has higher affinity for ligand, we introduced an N-glycosylation site to 'wedge open' the interface between the lectin and EGF-like domains of P-selectin. This alteration increased the affinity of P-selectin for its ligand Pselectin glycoprotein 1 (PSGL-1) and thereby the strength of P-selectin-mediated rolling adhesion. Similarly, an asparagine-to-glycine substitution in the lectin-EGF-like domain interface of L-selectin enhanced rolling adhesion under shear flow. Our results demonstrate that force, by 'favoring' an extended selectin conformation, can strengthen selectin-ligand bonds.Leukocyte migration to inflamed tissues and lymphocyte homing to peripheral lymphoid organs involves a multistep process 1-6 . In the first step, leukocytes tether and roll along vascular endothelia. Rolling exposes leukocytes to chemokines that activate integrins, which arrest leukocyte rolling and mediate leukocyte migration across the endothelia.Rolling results from the hydrodynamic drag force acting on adherent cells. For rolling to be stable, the formation of new receptor-ligand bonds downstream must balance the dissociation of bonds upstream. Leukocyte tethering and rolling are mediated mainly by E-, L-and Pselectins. By initiating transient, rapidly reversible receptor-ligand interactions, these C-type lectin molecules allow a 'zone of adhesion' to move along a vessel wall 7-9 . In contrast, antibody-antigen interactions are unable to support stable rolling over a wide range of shear stresses 10 .Two features contribute to the ability of selectins to mediate stable leukocyte rolling. First, force increases the number of bonds that form between a rolling cell and its substrate, which effectively compensates for the shortening of receptor-ligand bond lifetimes that occurs as force on the bond increases 11 . Cell deformation and tether extension also promote leukocyte rolling 11-13 . Second, individual selectin-ligand bonds are more resistant to force than any other measured receptor-ligand bond 8,11,14 . As force on the receptor-ligand bond increases, the 'off rate' (k off ) increases less for selectin-ligand bonds than for integrin-ligand orCorrespondence should be addressed to T.A.S. (springeroffice@cbr.med.harvard.edu).. Note: Supplementary information is available on the Nature Immunology website. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. Selectins contain an N-terminal calcium-dependent lectin domain, an epidermal growth factor (EGF)-like domain, a variable number of short consensus repeats (SCRs), and transmembrane and cytoplasmic domains 6,18-20 . Selectin ligands consist mainly of mucin-like sialoglycopro...

show abstract

The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide

Cited by 672 publications

References 44 publications

Adhesion molecules of allergic inflammation: recent insights into their functional roles

Adhesion molecules of allergic inflammation: recent insights into their functional roles

Mechanism of Human α-1,3-Fucosyltransferase V: Glycosidic Cleavage Occurs Prior to Nucleophilic Attack

Remodeling of the lectin–EGF-like domain interface in P- and L-selectin increases adhesiveness and shear resistance under hydrodynamic force

Contact Info

Product

Resources

About