Ligand and cation binding are dual functions of a discrete segment of the integrin beta 3 subunit: cation displacement is involved in ligand binding.
The alpha IIb beta 3 integrin binds Arg-Gly-Asp-containing (RGD-containing) ligands in a cation-dependent interaction. A fourteen amino acid sequence, beta 3 (118-131), and an antibody to it, inhibited ligand binding functions of alpha IIb beta 3, and a 1:1 stoichiometric beta 3 (118-131)-RGD complex was detected by mass spectroscopy. Cation binding to beta 3 (118-131) was demonstrated by terbium luminescence and mass spectroscopy. Notably, ligand displaced cation from the beta 3(118-131) peptide and also from purified alpha IIb beta 3. Thus, beta 3 (118-131), a highly conserved region in integrin beta subunits, binds both ligand and cation. Formation of a ternary complex between cation, ligand, and receptor, with subsequent displacement of cation from beta 3 (118-131) and a second site within the receptor, may be central to the mechanism of ligand recognition by integrins.
D'Souza
S E
SE
Department of Molecular Cardiology, Cleveland Clinic Foundation, Ohio 44195.
Haas
T A
TA
Piotrowicz
R S
RS
Byers-Ward
V
V
McGrath
D E
DE
Soule
H R
HR
Cierniewski
C
C
Plow
E F
EF
Smith
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002412:Cations; D006801:Humans; D006825:Hybridomas; D039661:Integrin beta3; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D010954:Plasmacytoma; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
D000911:Antibodies, Monoclonal; D002412:Cations; D039661:Integrin beta3; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid