LFA-1 binding site in ICAM-3 contains a conserved motif and non-contiguous amino acids.
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.
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- Transfection
- Sequence Deletion
- Recombinant Fusion Proteins
- Protein Structure, Secondary
- Mutagenesis, Site-Directed
- Molecular Sequence Data
- Microscopy, Electron
- Mice, Inbred BALB C
- Mice
- Lymphocyte Function-Associated Antigen-1
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transfection
- Sequence Deletion
- Recombinant Fusion Proteins
- Protein Structure, Secondary
- Mutagenesis, Site-Directed
- Molecular Sequence Data
- Microscopy, Electron
- Mice, Inbred BALB C
- Mice
- Lymphocyte Function-Associated Antigen-1