Scaffold-mediated nucleation of protein signaling complexes: elementary principles

DOI10.1016/J.MBS.2011.06.003zbMATH Open1218.92039arXiv1105.4688OpenAlexW2002269843WikidataQ35109787 ScholiaQ35109787MaRDI QIDQ554489FDOQ554489

Authors: Jin Yang, William S. Hlavacek 

Publication date: 4 August 2011

Published in: Mathematical Biosciences (Search for Journal in Brave)

Abstract: Proteins with multiple binding sites play important roles in cell signaling systems by nucleating protein complexes in which, for example, enzymes and substrates are co-localized. Proteins that specialize in this function are called by a variety names, including adapter, linker and scaffold. Scaffold-mediated nucleation of protein complexes can be either constitutive or induced. Induced nucleation is commonly mediated by a docking site on a scaffold that is activated by phosphorylation. Here, by considering minimalist mathematical models, which recapitulate scaffold effects seen in more mechanistically detailed models, we obtain analytical and numerical results that provide insights into scaffold function. These results elucidate how recruitment of a pair of ligands to a scaffold depends on the concentrations of the ligands, on the binding constants for ligand-scaffold interactions, on binding cooperativity, and on the milieu of the scaffold, as ligand recruitment is affected by competitive ligands and decoy receptors. For the case of a bivalent scaffold, we obtain an expression for the unique scaffold concentration that maximally recruits a pair of monovalent ligands. Through simulations, we demonstrate that a bivalent scaffold can nucleate distinct sets of ligands to equivalent extents when the scaffold is present at different concentrations. Thus, the function of a scaffold can potentially change qualitatively with a change in copy number. We also demonstrate how a scaffold can change the catalytic efficiency of an enzyme and the sensitivity of the rate of reaction to substrate concentration. The results presented here should be useful for understanding scaffold function and for engineering scaffolds to have desired properties.

Full work available at URL: https://arxiv.org/abs/1105.4688

Recommendations

• The interplay of double phosphorylation and scaffolding in MAPK pathways
• Spatially-localized scaffold proteins may facilitate to transmit long-range signals
• Mathematical modeling for multisite phosphorylation with scaffold binding in cell signaling
• Ligand-induced coupling versus receptor pre-association: cellular automaton simulations of FGF-2 binding
• A model and analysis of the AKAP scaffold

zbMATH Keywords

synthetic biologybiological design principlescombinatorial inhibitionmultivalent bindingprozone effectternary complex

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Probabilistic models, generic numerical methods in probability and statistics (65C20) Systems biology, networks (92C42)

Cites Work

• An introduction to systems biology. Design principles of biological circuits.
• Title not available (Why is that?)
• Design principles for elementary gene circuits: Elements, methods, and examples
• Receptor clustering on a cell surface. I. Theory of receptor cross- linking by ligands bearing two chemically identical functional groups
• Equilibrium binding of multivalent ligands to cells: Effects of cell and receptor density

Cited In (2)

• A general model of multivalent binding with ligands of heterotypic subunits and multiple surface receptors
• Spatially-localized scaffold proteins may facilitate to transmit long-range signals

This page was built for publication: Scaffold-mediated nucleation of protein signaling complexes: elementary principles

Report a bug (only for logged in users!)Click here to report a bug for this page (MaRDI item Q554489)