Critical residues of integrin αIIb subunit for binding of αIIbβ3 (glycoprotein IIb-IIIa) to fibrinogen and ligand-mimetic antibodies (PAC-1, OP-G2, and LJ-CP3)

Tetsuji Kamata, Atsushi Irie, Michihide Tokuhira, Yoshikazu Takada

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Integrin αIIbβ3 plays a critical role in platelet aggregation through its interaction with fibrinogen. Elucidation of the mechanisms of αIIbβ3- fibrinogen interaction is critical to understanding hemostasis and thrombosis. Here we report that mutations of Gly-184, Tyr-189, Tyr-190, Phe- 191, and Gly-193 within the predicted turn structure of the third amino- terminal repeat of αIIb significantly block binding of αIIbβ3 to soluble fibrinogen. These mutations also block binding of αIIbβ3 to ligand-mimetic monoclonal antibodies PAC-1, OP-G2, LJ-CP3, which have an RGD-related RYD sequence in their antigen-binding sites. These mutations do not significantly affect the expression of αIIbβ3, in contrast to most of the natural αIIb mutations occurring in Glanzmann's thrombasthenic patients. The data suggest that these residues are critically involved in αIIbβ3-ligand interactions.

Original languageEnglish (US)
Pages (from-to)18610-18615
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number31
DOIs
StatePublished - 1996
Externally publishedYes

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Platelet Glycoprotein GPIIb-IIIa Complex
Integrins
Fibrinogen
Ligands
Mutation
Antibodies
Terminal Repeat Sequences
Platelets
Agglomeration
Hemostasis
Binding Sites
Platelet Aggregation
Monoclonal Antibodies
Antigens
Thrombosis
2-carboxyarabinitol 1-phosphate

ASJC Scopus subject areas

  • Biochemistry

Cite this

Critical residues of integrin αIIb subunit for binding of αIIbβ3 (glycoprotein IIb-IIIa) to fibrinogen and ligand-mimetic antibodies (PAC-1, OP-G2, and LJ-CP3). / Kamata, Tetsuji; Irie, Atsushi; Tokuhira, Michihide; Takada, Yoshikazu.

In: Journal of Biological Chemistry, Vol. 271, No. 31, 1996, p. 18610-18615.

Research output: Contribution to journalArticle

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abstract = "Integrin αIIbβ3 plays a critical role in platelet aggregation through its interaction with fibrinogen. Elucidation of the mechanisms of αIIbβ3- fibrinogen interaction is critical to understanding hemostasis and thrombosis. Here we report that mutations of Gly-184, Tyr-189, Tyr-190, Phe- 191, and Gly-193 within the predicted turn structure of the third amino- terminal repeat of αIIb significantly block binding of αIIbβ3 to soluble fibrinogen. These mutations also block binding of αIIbβ3 to ligand-mimetic monoclonal antibodies PAC-1, OP-G2, LJ-CP3, which have an RGD-related RYD sequence in their antigen-binding sites. These mutations do not significantly affect the expression of αIIbβ3, in contrast to most of the natural αIIb mutations occurring in Glanzmann's thrombasthenic patients. The data suggest that these residues are critically involved in αIIbβ3-ligand interactions.",
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AU - Takada, Yoshikazu

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AB - Integrin αIIbβ3 plays a critical role in platelet aggregation through its interaction with fibrinogen. Elucidation of the mechanisms of αIIbβ3- fibrinogen interaction is critical to understanding hemostasis and thrombosis. Here we report that mutations of Gly-184, Tyr-189, Tyr-190, Phe- 191, and Gly-193 within the predicted turn structure of the third amino- terminal repeat of αIIb significantly block binding of αIIbβ3 to soluble fibrinogen. These mutations also block binding of αIIbβ3 to ligand-mimetic monoclonal antibodies PAC-1, OP-G2, LJ-CP3, which have an RGD-related RYD sequence in their antigen-binding sites. These mutations do not significantly affect the expression of αIIbβ3, in contrast to most of the natural αIIb mutations occurring in Glanzmann's thrombasthenic patients. The data suggest that these residues are critically involved in αIIbβ3-ligand interactions.

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