Transforming binding affinities from three dimensions to two with application to cadherin clustering

Yinghao Wu, Jeremie Vendome, Lawrence Shapiro, Avinoam Ben-Shaul, Barry Honig

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Membrane-bound receptors often form large assemblies resulting from binding to soluble ligands, cell-surface molecules on other cells and extracellular matrix proteins. For example, the association of membrane proteins with proteins on different cells (trans-interactions) can drive the oligomerization of proteins on the same cell (cis-interactions). A central problem in understanding the molecular basis of such phenomena is that equilibrium constants are generally measured in three-dimensional solution and are thus difficult to relate to the two-dimensional environment of a membrane surface. Here we present a theoretical treatment that converts three-dimensional affinities to two dimensions, accounting directly for the structure and dynamics of the membrane-bound molecules. Using a multiscale simulation approach, we apply the theory to explain the formation of ordered, junction-like clusters by classical cadherin adhesion proteins. The approach features atomic-scale molecular dynamics simulations to determine interdomain flexibility, Monte Carlo simulations of multidomain motion and lattice simulations of junction formation. A finding of general relevance is that changes in interdomain motion on trans-binding have a crucial role in driving the lateral, cis-, clustering of adhesion receptors.

Original languageEnglish (US)
Pages (from-to)510-513
Number of pages4
JournalNature
Volume475
Issue number7357
DOIs
StatePublished - Jul 28 2011
Externally publishedYes

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Cadherins
Cluster Analysis
Cell Communication
Membranes
Proteins
Extracellular Matrix Proteins
Molecular Dynamics Simulation
Membrane Proteins
Ligands

ASJC Scopus subject areas

  • General

Cite this

Transforming binding affinities from three dimensions to two with application to cadherin clustering. / Wu, Yinghao; Vendome, Jeremie; Shapiro, Lawrence; Ben-Shaul, Avinoam; Honig, Barry.

In: Nature, Vol. 475, No. 7357, 28.07.2011, p. 510-513.

Research output: Contribution to journalArticle

Wu, Yinghao ; Vendome, Jeremie ; Shapiro, Lawrence ; Ben-Shaul, Avinoam ; Honig, Barry. / Transforming binding affinities from three dimensions to two with application to cadherin clustering. In: Nature. 2011 ; Vol. 475, No. 7357. pp. 510-513.
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