Role of the beta-subunit arginine/lysine finger in integrin heterodimer formation and function

J Immunol. 2008 Feb 1;180(3):1713-8. doi: 10.4049/jimmunol.180.3.1713.


Formation of the integrin alphabeta heterodimer is essential for cell surface expression and function. At the core of the alphabeta interface is a conserved Arg/Lys "finger" from the beta-subunit that inserts into a cup-like "cage" formed of two layers of aromatic residues in the alpha-subunit. We evaluated the role of this residue in heterodimer formation in an alphaA-lacking and an alphaA-containing integrin alphaVbeta3 and alphaMbeta2 (CD11b/CD18), respectively. Arg261 of beta3 was mutated to Ala or Glu; the corresponding Lys252 of beta2 was mutated to Ala, Arg, Glu, Asp, or Phe; and the effects on heterodimer formation in each integrin examined by ELISA and immunoprecipitation in HEK 293 cells cotransfected with plasmids encoding the alpha- and beta-subunits. The Arg261Glu (but not Arg261Ala) substitution significantly impaired cell surface expression and heterodimer formation of alphaVbeta3. Although Lys252Arg, and to a lesser extent Lys252Ala, were well tolerated, each of the remaining substitutions markedly reduced cell surface expression and heterodimer formation of CD11b/CD18. Lys252Arg and Lys252Ala integrin heterodimers displayed a significant increase in binding to the physiologic ligand iC3b. These data demonstrate an important role of the Arg/Lys finger in formation of a stable integrin heterodimer, and suggest that subtle changes at this residue affect the activation state of the integrin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Arginine / chemistry
  • Arginine / genetics
  • CD11a Antigen / chemistry*
  • CD11a Antigen / physiology*
  • CD18 Antigens / chemistry*
  • CD18 Antigens / genetics
  • CD18 Antigens / physiology*
  • Cell Line
  • Cell Membrane / chemistry
  • Dimerization
  • Humans
  • Integrin beta3 / chemistry*
  • Integrin beta3 / genetics
  • Integrin beta3 / physiology*
  • Lysine / chemistry
  • Lysine / genetics
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / physiology


  • CD11a Antigen
  • CD18 Antigens
  • Integrin beta3
  • Protein Subunits
  • Arginine
  • Lysine