Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain

J Mol Biol. 1999 Sep 10;292(1):1-9. doi: 10.1006/jmbi.1999.3047.


The lymphocyte function-associated antigen (LFA-1) belongs to the family of beta2-integrins and plays an important role in T-cell activation and leukocyte migration to sites of inflammation. We report here that lovastatin, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor intercellular adhesion molecule-1. Using nuclear magnetic resonance spectroscopy and X-ray crystallography we show that the inhibitor binds to a highly conserved domain of the LFA-1 alpha-chain called the I-domain. The first three-dimensional structure of an integrin inhibitor bound to its receptor reveals atomic details for a hitherto unknown mode of LFA-1 inhibition. It also sheds light into possible mechanisms of LFA-1 mediated signalling and will support the design of novel anti-adhesive and immunosuppressive drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • CD11 Antigens / chemistry
  • CD11 Antigens / metabolism*
  • Cell Adhesion / drug effects
  • Crystallography, X-Ray
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lovastatin / pharmacology*
  • Lymphocyte Function-Associated Antigen-1 / chemistry
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Binding / drug effects
  • Protein Structure, Secondary
  • Tumor Cells, Cultured


  • CD11 Antigens
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1
  • Lovastatin