Cell surface biology mediated by low affinity multivalent protein–glycan interactions

Collins, Brian E.; Paulson, James C.

doi:10.1016/j.cbpa.2004.10.004

Cited by 307 publications

(240 citation statements)

References 65 publications

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“…It has been reported previously that endothelial cells increase gal-1 synthesis and export to the cell surface in the presence of inflammatory cytokines and that gal-1 is highly expressed by endothelial cells in inflamed lymph nodes (32). In addition, extracellular matrix can concentrate and present enough gal-1 to induce T cell apoptosis (42,43), suggesting that the amounts of gal-1 that can be found in the extracellular matrix could potentially be sufficient to affect the efficiency of envelope-mediated fusion.…”

Section: Discussionmentioning

confidence: 95%

Novel Innate Immune Functions for Galectin-1: Galectin-1 Inhibits Cell Fusion by Nipah Virus Envelope Glycoproteins and Augments Dendritic Cell Secretion of Proinflammatory Cytokines

Levroney

Aguilar

Fulcher

et al. 2005

The Journal of Immunology

150

159

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Galectin-1 (gal-1), an endogenous lectin secreted by a variety of cell types, has pleiotropic immunomodulatory functions, including regulation of lymphocyte survival and cytokine secretion in autoimmune, transplant disease, and parasitic infection models. However, the role of gal-1 in viral infections is unknown. Nipah virus (NiV) is an emerging pathogen that causes severe, often fatal, febrile encephalitis. The primary targets of NiV are endothelial cells. NiV infection of endothelial cells results in cell-cell fusion and syncytia formation triggered by the fusion (F) and attachment (G) envelope glycoproteins of NiV that bear glycan structures recognized by gal-1. In the present study, we report that NiV envelope-mediated cell-cell fusion is blocked by gal-1. This inhibition is specific to the Paramyxoviridae family because gal-1 did not inhibit fusion triggered by envelope glycoproteins of other viruses, including two retroviruses and a pox virus, but inhibited fusion triggered by envelope glycoproteins of the related Hendra virus and another paramyxovirus. The physiologic dimeric form of gal-1 is required for fusion inhibition because a monomeric gal-1 mutant had no inhibitory effect on cell fusion. gal-1 binds to specific N-glycans on NiV glycoproteins and aberrantly oligomerizes NiV-F and NiV-G, indicating a mechanism for fusion inhibition. gal-1 also increases dendritic cell production of proinflammatory cytokines such as IL-6, known to be protective in the setting of other viral diseases such as Ebola infections. Thus, gal-1 may have direct antiviral effects and may also augment the innate immune response against this emerging pathogen.

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Section: Discussionmentioning

confidence: 95%

Novel Innate Immune Functions for Galectin-1: Galectin-1 Inhibits Cell Fusion by Nipah Virus Envelope Glycoproteins and Augments Dendritic Cell Secretion of Proinflammatory Cytokines

Levroney

Aguilar

Fulcher

et al. 2005

The Journal of Immunology

150

159

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“…[10][11][12][13][14][15] The generation of high affinity ligands, however, is not trivial because the interaction of individual carbohydrate epitopes with lectins is in many cases weak and undiscriminating. 16 The binding affinity can be dramatically increased by clustering of lectin binding sites and carbohydrate recognition units. [17][18][19][20][21][22][23] The observation that the binding affinity increases exponentially with the number of binding sites has been termed the glycoside cluster effect.…”

Section: Introductionmentioning

confidence: 99%

Probing multivalent carbohydrate–lectin interactions by an enzyme-linked lectin assay employing covalently immobilized carbohydrates

Maierhofer

Rohmer

Wittmann

2007

Bioorganic & Medicinal Chemistry

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Abstract-We report here the synthesis of a series of mono-to trivalent N-acetylglucosamine (GlcNAc) derivatives as ligands for the plant lectin wheat germ agglutinin (WGA). Their WGA binding potencies were determined by an established enzyme-linked lectin assay (ELLA) employing microtiter plates with non-covalently immobilized porcine stomach mucin (PSM) as reference ligand and an ELLA with a new GlcNAc derivative covalently immobilized via a thiourea linkage. Comparison of both assays revealed that the type of presentation of GlcNAc residues on the microtiter plates either as part of a glycoprotein or as a covalently immobilized monosaccharide derivative strongly influences the outcome of the assay. Although the apparent dissociation constants K ELLA D for the interaction of peroxidase-labeled WGA with the microtiter plates are comparable for both surfaces, IC 50 values obtained with the PSM-free ELLA were substantially lower. Even more strikingly, this ELLA displayed a better differentiation between ligands of different valency leading to significantly higher relative inhibitory potencies of multivalent ligands compared to monovalent. Additionally, problems associated with the use of PSM, such as maximum inhibition at considerably less than 100% and poor reproducibility of IC 50 values could be overcome with this type of ELLA.

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“…Experiments indicate that such selective behavior can be obtained using multivalency (5)(6)(7)(8). During multivalent interactions a type of particle (henceforth referred to as the "guest") uses multiple ligands to bind simultaneously to several of the receptors displayed by another type of particle or surface (the "host") (9, 10).…”

mentioning

confidence: 99%

“…Mammen et al (9) recognized the importance of this type of system more than ten years ago. Since then, the concept of multivalency has found numerous applications in cell biology (7,11), supramolecular chemistry (10), nano-medicine (4,6), immunology (12,13), and cancer treatment (2,3,5,14), to name but a few examples. The work of Davis et al (3) provides a striking illustration of selective targeting achieved with multivalency: multivalent siRNA nano-particles administered to human patients were found to be selective in targeting cancer cells because the latter overexpress human-transferringprotein receptors.…”

mentioning

confidence: 99%

Designing super selectivity in multivalent nano-particle binding

Martínez-Veracoechea

Frenkel

2011

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

300

479

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A key challenge in nano-science is to design ligand-coated nanoparticles that can bind selectively to surfaces that display the cognate receptors above a threshold (surface) concentration. Nanoparticles that bind monovalently to a target surface do not discriminate sharply between surfaces with high and low receptor coverage. In contrast, "multivalent" nano-particles that can bind to a larger number of ligands simultaneously, display regimes of "super selectivity" where the fraction of bound particles varies sharply with the receptor concentration. We present numerical simulations that show that multivalent nano-particles can be designed such that they approach the "on-off" binding behavior ideal for receptor-concentration selective targeting. We propose a simple analytical model that accounts for the super selective behavior of multivalent nano-particles. The model shows that the super selectivity is due to the fact that the number of distinct ligand-receptor binding arrangements increases in a highly nonlinear way with receptor coverage. Somewhat counterintuitively, our study shows that selectivity can be improved by making the individual ligand-receptor bonds weaker. We propose a simple rule of thumb to predict the conditions under which super selectivity can be achieved. We validate our model predictions against the Monte Carlo simulations.ne of the key challenges in nano-medicine is to acquire the ability to design supramolecular constructs that can target surfaces that display a motif or receptor above a threshold concentration while leaving surfaces with lower coverage of such receptors unaffected (1-4). Experiments indicate that such selective behavior can be obtained using multivalency (5-8). During multivalent interactions a type of particle (henceforth referred to as the "guest") uses multiple ligands to bind simultaneously to several of the receptors displayed by another type of particle or surface (the "host") (9, 10). Mammen et al. (9) recognized the importance of this type of system more than ten years ago. Since then, the concept of multivalency has found numerous applications in cell biology (7, 11), supramolecular chemistry (10), nano-medicine (4, 6), immunology (12, 13), and cancer treatment (2,3,5,14), to name but a few examples. The work of Davis et al. There is a substantial body of theoretical work that aims to explain the pronounced enhancement in binding strength that certain multivalent systems can present in comparison with their monovalent counterparts (15-17). In particular, Kitov and Bundle (18) have pointed out that the strength of multivalent binding can be enhanced if there are many possible permutations in the binding pattern of receptors and ligands. The role of steric repulsion and conformational entropy in multivalent systems have been studied using molecular theories (19) and Monte Carlo (MC) simulations (20, 21). However, a unified picture that explains why high selectivity is observed in some experimental realizations of multivalent systems but not in others is still lacki...

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Cell surface biology mediated by low affinity multivalent protein–glycan interactions

Cited by 307 publications

References 65 publications

Novel Innate Immune Functions for Galectin-1: Galectin-1 Inhibits Cell Fusion by Nipah Virus Envelope Glycoproteins and Augments Dendritic Cell Secretion of Proinflammatory Cytokines

Novel Innate Immune Functions for Galectin-1: Galectin-1 Inhibits Cell Fusion by Nipah Virus Envelope Glycoproteins and Augments Dendritic Cell Secretion of Proinflammatory Cytokines

Probing multivalent carbohydrate–lectin interactions by an enzyme-linked lectin assay employing covalently immobilized carbohydrates

Designing super selectivity in multivalent nano-particle binding

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