Publications [#113168] of Harold P. Erickson

Papers Published

1. C Sadhu, B Lipsky, HP Erickson, J Hayflick, KO Dick, WM Gallatin, DE Staunton, LFA-1 binding site in ICAM-3 contains a conserved motif and non-contiguous amino acids., Cell adhesion and communication, SWITZERLAND, vol. 2 no. 5 (October, 1994), pp. 429-40, ISSN 1061-5385
   (last updated on 2009/02/12)

   Abstract:
   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.

   Keywords:
   Amino Acid Sequence • Animals • Antibodies, Monoclonal • Antigens, CD* • Antigens, Differentiation* • Base Sequence • Binding Sites • Cell Adhesion Molecules • Cell Line • Cercopithecus aethiops • Conserved Sequence • Epitopes • Lymphocyte Function-Associated Antigen-1 • Mice • Mice, Inbred BALB C • Microscopy, Electron • Molecular Sequence Data • Mutagenesis, Site-Directed • Protein Structure, Secondary* • Recombinant Fusion Proteins • Sequence Deletion • Transfection • analysis • chemistry • chemistry* • immunology • metabolism • metabolism* • ultrastructure