Signalosome assembly by domains undergoing dynamic head-to-tail polymerization

Trends Biochem Sci. 2014 Oct;39(10):487-95. doi: 10.1016/j.tibs.2014.08.006. Epub 2014 Sep 16.

Abstract

A key mechanism for guarding against inappropriate activation of signaling molecules is their weak affinity for effectors, which prevents them from undergoing accidental signal-transducing interactions due to fluctuations in their cellular concentration. The molecular devices that overcome these weak affinities are the signalosomes: dynamic clusters of transducing molecules assembled typically at signal-activated receptors. Signalosomes contain high local concentrations of protein-binding sites, and thus have a high avidity for their low-affinity ligands that generate signal responses. This review focuses on three domains - DIX (dishevelled and axin), PB1 (Phox and Bem1), and SAM (sterile alpha motif) - that undergo dynamic head-to-tail polymerization to assemble signalosomes and similar particles that require transient high local concentrations of protein-binding sites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • Monomeric GTP-Binding Proteins / metabolism
  • Protein Binding
  • Protein Multimerization*
  • Protein Structure, Tertiary
  • SAM Domain and HD Domain-Containing Protein 1
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Wnt Proteins / chemistry
  • Wnt Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Wnt Proteins
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Monomeric GTP-Binding Proteins