Specific interaction of the recombinant disintegrin-like domain of MDC- 15 (Metargidin, ADAM-15) with integrin αvβ3

Xi Ping Zhang, Tetsuji Kamata, Kenji Yokoyama, Wilma Puzon-McLaughlin, Yoshikazu Takada

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Abstract

MDC-15 (ADAM-15, metargidin), a membrane-anchored metalloprotease/disintegrin/cysteine-rich protein, is expressed on the surface of a wide range of cells and has an RGD tripeptide in its disintegrin-like domain. MDC-15 is potentially involved in cell-cell interactions through its interaction with integrins. We expressed a recombinant MDC-15 disintegrin-like domain as a fusion protein with glutathione S-transferase (designated D-15) in bacteria and examined its binding function to integrins using mammalian cells expressing different recombinant integrins. We found that D-15 specifically interacts with αvβ3 but not with the other integrins tested (α2β1, α3β1, α4β1, α5β1, α6β1, α6β4, αvβ1, αIIbβ3, and αLβ2). Mutation of the tripeptide RGD to SGA totally blocked binding of D-15 to αvβ3, suggesting that D-15- αvβ3 interaction is ROD-dependent. When the sequence RPTRGD is mutated to NWKRGD, D-15 is recognized by both αIIbβ3 and αvβ3, suggesting that the receptor binding specificity is mediated by the sequence flanking the RGD tripeptide, as in snake venom disintegrins. These results indicate that the disintegrin-like domain of MDC-15 functions as an adhesion molecule and may be involved n αvβ3-mediated cell-cell interactions.

Original languageEnglish
Pages (from-to)7345-7350
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number13
DOIs
Publication statusPublished - Mar 27 1998
Externally publishedYes

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Disintegrins
Integrins
Cell Communication
Snake Venoms
Metalloproteases
Glutathione Transferase
Cysteine
Bacteria
Proteins
Fusion reactions
Adhesion
Cells
Membranes
Mutation
Molecules
arginyl-glycyl-aspartic acid

ASJC Scopus subject areas

  • Biochemistry

Cite this

Specific interaction of the recombinant disintegrin-like domain of MDC- 15 (Metargidin, ADAM-15) with integrin αvβ3. / Zhang, Xi Ping; Kamata, Tetsuji; Yokoyama, Kenji; Puzon-McLaughlin, Wilma; Takada, Yoshikazu.

In: Journal of Biological Chemistry, Vol. 273, No. 13, 27.03.1998, p. 7345-7350.

Research output: Contribution to journalArticle

Zhang, Xi Ping ; Kamata, Tetsuji ; Yokoyama, Kenji ; Puzon-McLaughlin, Wilma ; Takada, Yoshikazu. / Specific interaction of the recombinant disintegrin-like domain of MDC- 15 (Metargidin, ADAM-15) with integrin αvβ3. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 13. pp. 7345-7350.
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