LFA-1 binding site in ICAM-3 contains a conserved motif and non-contiguous amino acids.

Journal Article (Journal Article)

The intercellular adhesion molecule-3 (ICAM-3) is a counter receptor for the integrin LFA-1 that supports cell-cell adhesion dependent functions. ICAM-3 is a member of the immunoglobulin superfamily possessing five immunoglobulin-like domains. Here, we characterize the overall shape of ICAM-3 and the amino acid residues involved in binding LFA-1 and monoclonal antibodies (Mab). Electron microscopic observations show that ICAM-3 is predominantly a straight rod of 15 nm in length, suggesting a head to tail arrangement of the immunoglobulin-like domains. Six out of nine ICAM-3 Mab described blocked the interaction with LFA-1 to varying degrees. Domain assignment of blocking Mab epitopes and characterization of LFA-1-dependent cell adhesion to ICAM-3 mutants demonstrate that the amino-terminal domain of ICAM-3 interacts with LFA-1. A conserved amino acid motif including residues E37 and T38 form an integrin binding site (IBS) in ICAM-3. This motif has also been shown to function as an IBS in ICAM-3 and VCAM-1 and hence many form a common site of contact in all CAMs of this type. Other ICAM-3 residues critical to adhesive interactions, such as Q75, conserved in ICAM-1 and ICAM-2, but not VCAM-1, may confer specificity to LFA-1 binding. This residue, Q75, is predicted to locate in a model of ICAM-3 to the same site as RGD in the immunoglobulin-like domain of fibronectin that binds several integrins. This suggest an evolutionary relationship between ICAMs and fibronectin interactions with integrins.

Full Text

Duke Authors

Cited Authors

  • Sadhu, C; Lipsky, B; Erickson, HP; Hayflick, J; Dick, KO; Gallatin, WM; Staunton, DE

Published Date

  • October 1994

Published In

Volume / Issue

  • 2 / 5

Start / End Page

  • 429 - 440

PubMed ID

  • 7531103

International Standard Serial Number (ISSN)

  • 1061-5385

Digital Object Identifier (DOI)

  • 10.3109/15419069409004453


  • eng

Conference Location

  • Switzerland