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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Vineet GuptaM Amin Arnaout

Abstract

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...Continue Reading

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Citations

Sep 15, 2009·The Biochemical Journal·A Paul MouldMartin J Humphries
Jul 3, 2009·Journal of Leukocyte Biology·William M McKillopGregory A Dekaban
May 3, 2015·Journal of Leukocyte Biology·Ileana Licona-LimónEnrique Ortega
Mar 1, 2019·International Journal of Molecular Sciences·Michaela FrolikovaKaterina Dvorakova-Hortova
Nov 2, 2019·Journal of Medicinal Chemistry·Giulia MartelliDaria Giacomini

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