Specific binding of integrin αvβ3 to the fibrinogen γ and α(E) chain C-terminal domains

Kenji Yokoyama, Xi Ping Zhang, Leonid Medved, Yoshikazu Takada

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Integrin αvβ3, a widely distributed fibrinogen receptor, recognizes the RGD572-574 motif in the α chain of human fibrinogen. However, this motif is not conserved in other species, nor is it required for αvβ3- mediated fibrin clot retraction, suggesting that fibrinogen may have other αvβ3 binding sites. Fibrinogen has conserved C-terminal domains in its α (E variant), β, and γ chains (designated α(E)C, βC, and γC, respectively), but their function in cell adhesion is not known, except that αIIbβ3, a platelet fibrinogen receptor, binds to the γC HHLGGAKQAGDV400-411 sequence. Here we used mammalian cells expressing recombinant αvβ3 to show that recombinant α(EC) and γC domains expressed in bacteria specifically bind to αvβ3. Interaction between αvβ3 and γC or α(E)C is blocked by LM609, a function-blocking anti-αvβ3 mAb, and by RGD peptides. αvβ3 does not require the HHLGGAKQAGDV400-411 sequence of γC for binding, and α(E)C does not have such a sequence, indicating that the αvβ3 binding sites are distinct from those of αIIbβ3. A small fragment of γC (residues 148-226) supports αvβ3 adhesion, suggesting that an αvβ3 binding site is located within the γ chain 148-226 region. We have reported that the CYDMKTTC sequence of β3 is responsible for the ligand specificity of αvβ3. γC and α(E)C do not bind to wild-type αvβ1, but do bind to the αvβ1 mutant (αvβ1-3-1), in which the CYDMKTTC sequence of β3 is substituted for the corresponding β1 sequence CTSEQNC. This suggests that γC and α(E)C contain determinants for fibrinogen's specificity to αvβ3. These results suggest that fibrinogen has potentially significant novel αvβ3 binding sites in γC and α(E)C.

Original languageEnglish
Pages (from-to)5872-5877
Number of pages6
JournalBiochemistry
Volume38
Issue number18
DOIs
Publication statusPublished - May 4 1999
Externally publishedYes

Fingerprint

Integrins
Fibrinogen
Binding Sites
Fibrinogen Receptors
Clot Retraction
Cell adhesion
Platelets
Fibrin
Cell Adhesion
Bacteria
Blood Platelets
Adhesion
Cells
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Specific binding of integrin αvβ3 to the fibrinogen γ and α(E) chain C-terminal domains. / Yokoyama, Kenji; Zhang, Xi Ping; Medved, Leonid; Takada, Yoshikazu.

In: Biochemistry, Vol. 38, No. 18, 04.05.1999, p. 5872-5877.

Research output: Contribution to journalArticle

Yokoyama, Kenji ; Zhang, Xi Ping ; Medved, Leonid ; Takada, Yoshikazu. / Specific binding of integrin αvβ3 to the fibrinogen γ and α(E) chain C-terminal domains. In: Biochemistry. 1999 ; Vol. 38, No. 18. pp. 5872-5877.
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