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 language | English |
|---|---|
| Pages (from-to) | 17804-17810 |
| Number of pages | 7 |
| Journal | Journal of Biological Chemistry |
| Volume | 277 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - May 17 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Functional classification of ADAMs based on a conserved motif for binding to integrin α9β1. Implications for sperm-egg binding and other cell interactions. / Eto, Koji; Huet, Clotilde; Tarui, Takehiko; Kupriyanov, Sergey; Liu, Hai Zhen; Puzon-McLaughlin, Wilma; Zhang, Xi Ping; Sheppard, Dean; Engvall, Eva; Takada, Yoshikazu.
In: Journal of Biological Chemistry, Vol. 277, No. 20, 17.05.2002, p. 17804-17810.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Functional classification of ADAMs based on a conserved motif for binding to integrin α9β1. Implications for sperm-egg binding and other cell interactions
AU - Eto, Koji
AU - Huet, Clotilde
AU - Tarui, Takehiko
AU - Kupriyanov, Sergey
AU - Liu, Hai Zhen
AU - Puzon-McLaughlin, Wilma
AU - Zhang, Xi Ping
AU - Sheppard, Dean
AU - Engvall, Eva
AU - Takada, Yoshikazu
PY - 2002/5/17
Y1 - 2002/5/17
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M200086200
DO - 10.1074/jbc.M200086200
M3 - Article
VL - 277
SP - 17804
EP - 17810
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 20
ER -