The effect of receptor clustering on diffusion-limited forward rate constants

Goldstein, Byron; Wiegel, F.W.

doi:10.1016/s0006-3495(83)84330-6

Cited by 32 publications

(16 citation statements)

References 9 publications

(14 reference statements)

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“…Second, if the rafts are of the same or similar size as the virus particle, then virus particle binding to a raft-associated receptor can block the remaining free receptors in the raft from binding other virus particles. Our findings here for viral particle binding are consistent with earlier models that have shown how receptor clustering can reduce the rate of ligand binding to the cell surface (Goldstein and Wiegel, 1983;van Opheusden et al, 1984). Such inhibitory effects of receptor clustering on ligand binding provide a mechanism for understanding why the association of epidermal growth factor receptor (EGFR) with lipid rafts decreased EGF binding to the receptor (Lim and Yin, 2005;Roepstorff et al, 2002).…”

Section: Raft-mediated Receptor Clustering Inhibits Hiv-1 Bindingsupporting

confidence: 90%

Dynamic tradeoffs in the raft‐mediated entry of human immunodeficiency virus type 1 into cells

Lim

Yin

2005

Biotech & Bioengineering

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To initiate an infection human immunodeficiency virus type 1 (HIV-1) particles must first bind to receptors on the surface of their host cells, a process that eventually leads to fusion of viral and cellular membranes and release of the viral genome into the cytoplasm. Understanding the molecular mechanisms of these processes may enable the development of new anti-HIV strategies. Disagreement currently prevails on the role in virus entry of microdomains within the cellular plasma membrane known as lipid rafts. Experiments have suggested that lipid rafts, in their interactions with cellular receptors and viral particles, either promote or have minimal effect on viral entry. Here we develop a dynamic model for HIV-1 entry that enables us to identify and quantitatively assess tradeoffs that can arise from the clustering of receptors in rafts. Specifically, receptor clustering can be detrimental to the initiation of viral infection by reducing the probability that a virus particle finds its primary receptor, CD4. However, receptor clustering can also enable a virus particle, once bound, to rapidly form multivalent interactions with receptors and co-receptors that are required for virus-cell membrane fusion. We show how the resolution of such tradeoffs hinges on the level and spatial distribution of receptors and co-receptors on the cell surface, and we discuss implications of these effects for the design of therapeutics that inhibit HIV-1 entry.

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Section: Raft-mediated Receptor Clustering Inhibits Hiv-1 Bindingsupporting

confidence: 90%

Dynamic tradeoffs in the raft‐mediated entry of human immunodeficiency virus type 1 into cells

Lim

Yin

2005

Biotech & Bioengineering

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“…Thus. these expressions are valid for arbitrary surface geometry of the cell and its receptors_ In this sense this paper forms a generalisation of the work of Goldstein and Wiegel [3].…”

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confidence: 81%

“…where l 0 is the permittivity of a vacuum [1,3]. The extra factor of 2 appears because for J we are concerned only with the receptors, while C includes their mirror images.…”

Section: J=jz=2jo-jmentioning

confidence: 99%

Forward rate constants for receptor clusters variational methods for upper and lower bounds

Opheusden

Wiegel

Goldstein

1984

Biophysical Chemistry

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We are interested in the effect of receptor clustering on k, , the diffusion-limited forward rate constant for the binding of a ligand to a cell surface receptor. Here we estimate the reduction in k, when receptors are clustered in various configuration;. We obtain two alternative expressions for the flux of ligands into receptors distributed on a surface. Next we show through a variational principle that these provide both upper and lower bounds on the fux when evaluated for trial concentration functions which satisfy only the boundary conditions of the Laplace equation. We use an analogy with electrostatics to calculate rigorous bounds within approx. 10% of the exact result for a variety of planar clusters of hemispherical receptor sites. We also obtain an exact result for the flux into a spheroidal receptor and use this result to obtain bounds on the flux into certain receptor clusters.

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“…The forward and reverse rate constants for binding to clustered receptors will be reduced compared to the rate constants for binding to non clustered receptors, although the equilibrium constants will be unaltered (Goldstein and Weigel, 1983). In terms of the parameters shown in Figure 8, in the diffusion At 37°C a bound ligand can leave the cell surface not only by dissociating from the receptor, but also by being internalized with it.…”

Section: The Interaction Of Ligands With Receptorsmentioning

confidence: 99%