Mapping of potent and specific binding motifs, GLOGEN and GVOGEA, for integrin α1β1 using collagen toolkits II and III

J Biol Chem. 2012 Jul 27;287(31):26019-28. doi: 10.1074/jbc.M112.353144. Epub 2012 May 31.

Abstract

Integrins are well characterized cell surface receptors for extracellular matrix proteins. Mapping integrin-binding sites within the fibrillar collagens identified GFOGER as a high affinity site recognized by α2β1, but with lower affinity for α1β1. Here, to identify specific ligands for α1β1, we examined binding of the recombinant human α1 I domain, the rat pheochromocytoma cell line (PC12), and the rat glioma Rugli cell line to our collagen Toolkit II and III peptides using solid-phase and real-time label-free adhesion assays. We observed Mg(2+)-dependent binding of the α1 I domain to the peptides in the following rank order: III-7 (GLOGEN), II-28 (GFOGER), II-7 and II-8 (GLOGER), II-18 (GAOGER), III-4 (GROGER). PC12 cells showed a similar profile. Using antibody blockade, we confirmed that binding of PC12 cells to peptide III-7 was mediated by integrin α1β1. We also identified a new α1β1-binding activity within peptide II-27. The sequence GVOGEA bound weakly to PC12 cells and strongly to activated Rugli cells or to an activated α1 I domain, but not to the α2 I domain or to C2C12 cells expressing α2β1 or α11β1. Thus, GVOGEA is specific for α1β1. Although recognized by both α2β1 and α11β1, GLOGEN is a better ligand for α1β1 compared with GFOGER. Finally, using biosensor assays, we show that although GLOGEN is able to compete for the α1 I domain from collagen IV (IC(50) ∼3 μm), GFOGER is much less potent (IC(50) ∼90 μm), as shown previously. These data confirm the selectivity of GFOGER for α2β1 and establish GLOGEN as a high affinity site for α1β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Binding, Competitive
  • Cell Adhesion
  • Collagen Type II / chemistry*
  • Collagen Type II / metabolism
  • Collagen Type III / chemistry*
  • Collagen Type III / metabolism
  • Collagen Type IV / chemistry
  • Humans
  • Integrin alpha1beta1 / chemistry*
  • Integrin alpha1beta1 / metabolism
  • Integrin alpha2 / chemistry
  • Mice
  • Molecular Sequence Data
  • PC12 Cells
  • Peptide Fragments / chemistry*
  • Peptide Mapping
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Rats

Substances

  • Collagen Type II
  • Collagen Type III
  • Collagen Type IV
  • Integrin alpha1beta1
  • Integrin alpha2
  • Peptide Fragments