A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1 - PubMed (original) (raw)
A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1
J M Casasnovas et al. Proc Natl Acad Sci U S A. 1998.
Abstract
The 3.0-A structure of a 190-residue fragment of intercellular adhesion molecule-1 (ICAM-1, CD54) reveals two tandem Ig-superfamily (IgSF) domains. Each of two independent molecules dimerizes identically with a symmetry-related molecule over a hydrophobic interface on the BED sheet of domain 1, in agreement with dimerization of ICAM-1 on the cell surface. The residues that bind to the integrin LFA-1 are well oriented for bivalent binding in the dimer, with the critical Glu-34 residues pointing away from each other on the periphery. Residues that bind to rhinovirus are in the flexible BC and FG loops at the tip of domain 1, and these and the upper half of domain 1 are well exposed in the dimer for docking to virus. By contrast, a residue important for binding to Plasmodium falciparum-infected erythrocytes is in the dimer interface. The presence of A' strands in both domains 1 and 2, conserved hydrogen bonds at domain junctions, and elaborate hydrogen bond networks around the key integrin binding residues in domain 1 make these domains suited to resist tensile forces during adhesive interactions. A subdivision of the intermediate (I) set of IgSF domains is proposed in which domain 1 of ICAM-1 and previously described I set domains belong to the I1 set and domain 2 of ICAM-1, ICAM-2, and vascular cell adhesion molecule-1 belong to the I2 set.
Figures
Figure 1
The crystal structure of the N-terminal two domains of ICAM-1. (A) Ribbon diagram (39) with β-strands in red, α-helix in blue, and coil in orange. The last residue of domain 1 (Tyr-83) is rose. N-linked sugars (yellow), Glu-37 in strand C of domain 1 (black), and disulfide bonds (green) are included. The last two residues of the structure are omitted. (B) Movement between domains 1 and 2 and comparison of domain 1 of molecules A and B. The Cα backbones of ICAM-1 molecules A (magenta) and B (yellow) are shown after superposition on domain 1. (C) Hydrogen bonds at the boundary between domains 1 and 2.
Figure 2
Domain structure. (A) Structural alignment of ICAM-1 with ICAM-2 and VCAM-1. β-strands defined by DSSP (31) for ICAM-1 molecules A or B, for ICAM-2 (16), and the longer form of VCAM-1 (17) are overlined. The α carbons of molecules A and B of ICAM-1, ICAM-2, and molecule A of VCAM-1 were structurally aligned with
3dmalign
of
modeller
(
http://guitar.rockefeller.edu/modeller/modeller.html
) with a gap penalty of 1.75 Å, separately for domain 1 and 2. Residues are in lowercase in ICAM-1 if they are not within 3.5 Å in molecules A and B, and in ICAM-2 and VCAM-1 if they are not within 1.75 Å of the framework (the average position of capitalized residues including both molecules A and B of ICAM-1). ICAM-1 residues in the dimer interface in domain 1 are asterisked, and a dot marks every 10th residue. N-linked glycosylation sites are boxed. (B) β-sheet frameworks. β-sheet framework residues in ICAM-1 are solid circles if defined as β-strand in molecules A or B by DSSP (31). Open circles represent conserved loop structures. Backbone hydrogen bonds are dashed lines and are shown if ≥1.0 kcal/mol with DSSP or found with
look
(Molecular Applications Group, Palo Alto, CA).
Figure 2
Domain structure. (A) Structural alignment of ICAM-1 with ICAM-2 and VCAM-1. β-strands defined by DSSP (31) for ICAM-1 molecules A or B, for ICAM-2 (16), and the longer form of VCAM-1 (17) are overlined. The α carbons of molecules A and B of ICAM-1, ICAM-2, and molecule A of VCAM-1 were structurally aligned with
3dmalign
of
modeller
(
http://guitar.rockefeller.edu/modeller/modeller.html
) with a gap penalty of 1.75 Å, separately for domain 1 and 2. Residues are in lowercase in ICAM-1 if they are not within 3.5 Å in molecules A and B, and in ICAM-2 and VCAM-1 if they are not within 1.75 Å of the framework (the average position of capitalized residues including both molecules A and B of ICAM-1). ICAM-1 residues in the dimer interface in domain 1 are asterisked, and a dot marks every 10th residue. N-linked glycosylation sites are boxed. (B) β-sheet frameworks. β-sheet framework residues in ICAM-1 are solid circles if defined as β-strand in molecules A or B by DSSP (31). Open circles represent conserved loop structures. Backbone hydrogen bonds are dashed lines and are shown if ≥1.0 kcal/mol with DSSP or found with
look
(Molecular Applications Group, Palo Alto, CA).
Figure 3
The dimer interface and ligand-binding residues. (A) Interacting residues in domain 1. Side chains are shown for residues that interact across the dimer interface in domain 1 (Fig. 2_A_). The conserved central Val-51 residue is blue, and Glu-34 is red. Salt bridges between residues at the periphery of the interface are dashed lines. (B) Stereoview (40) of the dimer. Side chains and α carbons are shown for residues important in binding to LFA-1 (red and orange) (3, 37), human rhinoviruses 3, 14, 15, 36, and 41 (yellow and orange) (–5), and P. falciparum (blue) (6). Only single amino acid substitutions that reduced binding 50% or 2 SD below control are shown.
Figure 4
A model for the ICAM-1 dimer on the cell surface. Domains 1 and 2 and their orientation in the dimer are from the crystal structure. The rod-like shape of domains 1–5 in the monomer and the bend between domains 3 and 4 are from electron microscopy (3, 36). Dimerization or proximity between domain 5 is based on hindrance of antibody binding to this domain in the dimer (25), and association at the transmembrane domain is based on its role in dimerization (24, 25).
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