Integrin α Dβ 2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties

Valentin P. Yakubenko, Satya P. Yadav, Tatiana P. Ugarova

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Integrin α Dβ 2, the most recently discovered member of the β2 subfamily of integrin adhesion receptors, is up-regulated on macrophage foam cells. Although other members of the subfamily have been subjects of extensive research, the recognition specificity and the molecular basis for α Dβ 2 ligand binding remain unknown. Based on the high extent of structural homology between α Dβ 2 and the major myeloid-cell-specific integrin α Mβ 2 (Mac-1), noted for its capacity to bind multiple ligands, we considered that the 2 integrins have similar recognition specificity. In this study, using recombinant and natural α Dβ 2-expressing cells, we demonstrate that α Dβ 2 supports adhesion and migration to many extracellular matrix proteins in a fashion similar to α Mβ 2. Consistent with these data, the recombinant α DI- domain of the receptor bound selected ligands. The binding was activation-dependent because the α DI-domain with its C-terminal α7 helix truncated, but not the form with the C-terminal part extended, bound ligands. When the α DI-domain segment Lys 244-Lys 260 (highly homologous to its α MI- domain counterpart Lys 245-Arg 261 responsible for α Mβ 2 multiligand-binding properties) was inserted into the monospecific α LI-domain, the chimeric protein bound many ligands with affinities similar to those of wild-type α DI-domain. These results establish integrin α Dβ 2 as a multiligand receptor and indicate that the mechanism whereby α Dβ 2 exhibits broad ligand specificity resembles that used by α Mβ 2, the most promiscuous member of the integrin family.

Original languageEnglish (US)
Pages (from-to)1643-1650
Number of pages8
JournalBlood
Volume107
Issue number4
DOIs
StatePublished - Feb 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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