Functional classification of ADAMs based on a conserved motif for binding to integrin α9β1. Implications for sperm-egg binding and other cell interactions

Koji Eto, Clotilde Huet, Takehiko Tarui, Sergey Kupriyanov, Hai Zhen Liu, Wilma Puzon-McLaughlin, Xi Ping Zhang, Dean Sheppard, Eva Engvall, Yoshikazu Takada

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

ADAMs (a disintegrin and metalloproteases) are members of the metzincin superfamily of metalloproteases. Among integrins binding to disintegrin domains of ADAMs are αvβ1 and αvβ3 and they bind in an RGD-independent and an RGD-dependent manner, respectively. Human ADAM15 is the only ADAM with the RGD motif in the disintegrin domain. Thus, both integrin α9β1 and αvβ3 recognize the ADAM15 disintegrin domain. We determined how these integrins recognize the ADAM15 disintegrin domain by mutational analysis. We found that the Arg481 and the Asp-Leu-Pro-Glu-Phe residues (residues 488-492) were critical for α9β3 binding, but the RGD motif (residues 484-486) was not. In contrast, the RGD motif was critical for αvβ3 binding, but the other residues flanking the RGD motif were not. As the RX6DLPEF α9β1 recognition motif (residues 481-492) is conserved among ADAMs, except for ADAM10 and 17, we hypothesized that α9β1 may recognize disintegrin domains in all ADAMs except ADAM10 and 17. Indeed we found that α9β1 bound avidly to the disintegrin domains of ADAM1, 2, 3, and 9 but not to the disintegrin domains of ADAM10 and 17. As several ADAMs have been implicated in sperm-oocyte interaction, we tested whether the functional classification of ADAMs, based on specificity for integrin α9β1, applies to sperm-egg binding. We found that the ADAM2 and 15 disintegrin domains bound to oocytes, but the ADAM17 disintegrin domain did not. Furthermore, the ADAM2 and 15 disintegrin domains effectively blocked binding of sperm to oocytes, but the ADAM17 disintegrin domain did not. These results suggest that oocytes and α9β1 have similar binding specificities for ADAMs and that α9β1, or a receptor with similar specificity, may be involved in sperm-egg interaction during fertilization. As α9β1 is a receptor for many ADAM disintegrins and α9β1 and ADAMs are widely expressed, α9β1-ADAM interaction may be of a broad biological importance.

Original languageEnglish (US)
Pages (from-to)17804-17810
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number20
DOIs
StatePublished - May 17 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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