Casasnovas, Jose M.;
Pieroni, Cristiana;
Springer, Timothy A.
Lymphocyte Function-Associated Antigen-1 Binding Residues in Intercellular Adhesion Molecule-2 (ICAM-2) and the Integrin Binding Surface in the ICAM Subfamily
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Lymphocyte Function-Associated Antigen-1 Binding Residues in Intercellular Adhesion Molecule-2 (ICAM-2) and the Integrin Binding Surface in the ICAM Subfamily
Contributor:
Casasnovas, Jose M.;
Pieroni, Cristiana;
Springer, Timothy A.
imprint:
National Academy of Sciences of the United States of America, 1999
Published in:Proceedings of the National Academy of Sciences of the United States of America
Language:
English
ISSN:
0027-8424
Origination:
Footnote:
Description:
<p>The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed significant differences in the presentation of the critical acidic residue important for integrin binding between I and non-I-domain integrin ligands. Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1). The integrin binding site runs diagonally across the GFC β -sheet and includes residues on the CD edge of the β -sandwich. The site is oblong and runs along a flat ridge on the upper half of domain 1, which is proposed to dock to a groove in the I domain of LFA-1, with the critical Glu-37 residue ligating the Mg<sup>2+</sup>in the I domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites. By contrast, major differences are seen with vascular cell adhesion molecule-1 (VCAM-1), which binds α<sub>4</sub>integrins that lack an I domain. The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1.</p>