Structural specializations of immunoglobulin superfamily members for adhesion to integrins and viruses.
The circulation and migration of leukocytes are critical for immune surveillance and immune response to infection or injury. The key step of leukocyte recruitment involves the adhesion between immunoglobulin superfamily (IgSF) proteins on endothelium and integrin molecules on leukocyte surfaces. Some of the IgSF members are subverted as virus receptors. Four crystal structures of N-terminal two-domain fragments of these IgSF proteins have been determined: intercellular adhesion molecule-1 (ICAM-1), ICAM-2, vascular adhesion molecule-1 (VCAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). An acidic residue near the bottom of domain 1 plays a key role in integrin binding. For ICAM-1 and ICAM-2, this glutamic acid residue is located on a flat surface, complementary to the flat surface of the I domain of the integrin to which they bind, lymphocyte function-associated antigen-1 (LFA-1). For VCAM-1 and MAdCAM-1, the acidic residue is aspartic acid, and it resides on a protruded CD loop which may be complementary to a more pocket-like structure in the alpha 4 integrins to which they bind, which lack I domains. A number of unique structural features of this subclass of IgSF have been identified which are proposed to consolidate the domain structure to resist force during adhesion to integrins. Different mechanisms are proposed for the different CAMs to present the integrin-binding surface toward the opposing cell for adhesion, and prevent cis interaction with integrins on the same cell. Finally, CD4 and ICAM-1 are compared in the context of ligand binding and virus binding, which shows how human immunodeficiency virus and rhinovirus fit well with the distinct structural feature of their cognate receptors.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussetts, USA.
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Wang
T A
TA
Springer
D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology*; D016023:Integrins / Q000737:chemistry / Q000276:immunology*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry / Q000276:immunology; D014780:Viruses / Q000276:immunology*
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; D008024:Ligands; D008565:Membrane Proteins; D011991:Receptors, Virus