Binding specificity of multiprotein signaling complexes is determined by both cooperative interactions and affinity preferences

Jon C D Houtman; Yuichiro Higashimoto; Nazzareno Dimasi; Sangwoo Cho; Hiroshi Yamaguchi; Brent Bowden; Carole Regan; Emilio L Malchiodi; Roy Mariuzza; Peter Schuck; Ettore Appella; Lawrence E Samelson

doi:10.1021/bi0357311

Binding specificity of multiprotein signaling complexes is determined by both cooperative interactions and affinity preferences

Biochemistry. 2004 Apr 13;43(14):4170-8. doi: 10.1021/bi0357311.

Authors

Jon C D Houtman¹, Yuichiro Higashimoto, Nazzareno Dimasi, Sangwoo Cho, Hiroshi Yamaguchi, Brent Bowden, Carole Regan, Emilio L Malchiodi, Roy Mariuzza, Peter Schuck, Ettore Appella, Lawrence E Samelson

Affiliation

¹ Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

PMID: 15065860
DOI: 10.1021/bi0357311

Abstract

The generation of multiprotein complexes at receptors and adapter proteins is crucial for the activation of intracellular signaling pathways. In this study, we used multiple biochemical and biophysical methods to examine the binding properties of several SH2 and SH3 domain-containing signaling proteins as they interact with the adapter protein linker for activation of T-cells (LAT) to form multiprotein complexes. We observed that the binding specificity of these proteins for various LAT tyrosines appears to be constrained both by the affinity of binding and by cooperative protein-protein interactions. These studies provide quantitative information on how different binding parameters can determine in vivo binding site specificity observed for multiprotein signaling complexes.

Publication types

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

MeSH terms

Adaptor Proteins, Signal Transducing*
Animals
Binding Sites
Carrier Proteins / chemistry
Carrier Proteins / physiology
Circular Dichroism
GRB2 Adaptor Protein
Intracellular Fluid / chemistry*
Intracellular Fluid / metabolism*
Intracellular Fluid / physiology
Macromolecular Substances
Membrane Proteins / chemistry
Membrane Proteins / physiology
Mice
Peptide Fragments / chemistry*
Peptide Fragments / metabolism
Peptide Fragments / physiology*
Phospholipase C gamma
Phosphopeptides / chemistry
Phosphopeptides / physiology
Phosphoproteins / chemistry
Phosphoproteins / physiology
Phosphorylation
Protein Binding
Proteins / chemistry
Proteins / physiology
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Signal Transduction*
Structure-Activity Relationship
Thermodynamics
Type C Phospholipases / chemistry
Type C Phospholipases / physiology
Tyrosine / chemistry

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
GRB2 Adaptor Protein
Grb2 protein, mouse
Lat protein, mouse
Macromolecular Substances
Membrane Proteins
Mona protein, mouse
Peptide Fragments
Phosphopeptides
Phosphoproteins
Proteins
Recombinant Proteins
SLP-76 signal Transducing adaptor proteins
Tyrosine
Type C Phospholipases
Phospholipase C gamma