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Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques
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Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques

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Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface

J M Casasnovas1, T A Springer, J H Liu

  • 1The Center for Blood Research, Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA.

Nature
|May 15, 1997
PubMed

Insights

The crystal structure of intercellular adhesion molecule-2 (ICAM-2) reveals key differences in how integrins with and without

Area of Science:

  • Cellular adhesion
  • Structural biology
  • Immunology

Background:

  • Integrin proteins mediate cell-cell and cell-extracellular matrix interactions.
  • Known integrin ligand structures (fibronectin, VCAM-1) involve integrins lacking 'I' domains.
  • Intercellular adhesion molecules (ICAMs) are recognized by 'I' domain-containing integrins like lymphocyte-function-associated antigen 1 (LFA-1).

Purpose of the Study:

  • To determine the crystal structure of the extracellular region of ICAM-2.
  • To elucidate the structural basis for LFA-1 recognition of ICAM-2.
  • To compare recognition site architectures between 'I' domain-containing and 'I' domain-lacking integrin-ligand interactions.

Main Methods:

  • X-ray crystallography to determine the three-dimensional structure of ICAM-2.
  • Structural analysis to identify key residues and features involved in LFA-1 binding.
  • Comparative structural modeling of ICAM-1 based on the ICAM-2 structure.

Main Results:

  • The crystal structure of the extracellular region of ICAM-2 was determined.
  • Glutamic acid at position 37 (Glu 37) in ICAM-2 is critical for LFA-1 binding and may coordinate the Mg2+ ion in the LFA-1 'I' domain.
  • ICAM-2 presents a relatively flat recognition surface with Glu 37 in a beta-strand, contrasting with protruding loops in fibronectin and VCAM-1.

Conclusions:

  • Structural differences in recognition sites exist between integrins with and without 'I' domains.
  • A bend between ICAM-2 domains and N-linked glycans may facilitate LFA-1 binding.
  • The ICAM-2 structure provides a model for understanding ICAM-1 recognition and potential pathogen interactions.

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