Functional Classification of ADAMs Based on a Conserved Motif for Binding to Integrin α9β1

By K. Eto, Clotilde Huet, T. Tarui, S. Kupriyanov, Hai-Zhen Liu, W. Puzon‐McLaughlin, Xi-ping Zhang, D. Sheppard, E. Engvall, Y. Takada. Journal of Biological Chemistry, 2002

158 citations recorded by the source corpus.

ADAMs (a disintegrin and metalloproteases) are members of the metzincin superfamily of metalloproteases. Among integrins binding to disintegrin domains of ADAMs are α9β1 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 α9β1 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 RX 6DLPEF α9β1recognition 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.

Subfields: Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e6fbc6b49ca1fb048b065b84b0078f886ef7288d

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In Immunology and Allergy

S. Takeda

In Molecular Biology

Citations in the corpus

The ADAMs family of metalloproteases: multidomain proteins with multiple functions. (2003, background): “Many ADAMs share a sequence (Rx6DEVF) in the disintegrin domain that, when mutated, inhibits the association with 9 1integrins (Eto et al. 2002).”
Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its unique C‐shaped scaffold (2006, background): “…for the VAP1 D/C-domains) might reveal additional protein–protein interaction interfaces other than the HVR. Multiple charged residues in the D-domain are essential for ADAM28 binding to a4b1 (Bridges et al, 2003) and the RX6DLPEF motif has been proposed for integrin a9b1 binding (Eto et al, 2002).”
The cysteine-rich domain regulates ADAM protease function in vivo (2002, background): “The Rockefeller University Press, 0021-9525/2002/12/893/10 $5.00 The Journal of Cell Biology, Volume 159, Number 5, December 9, 2002 893–902 http://www.jcb.org/cgi/doi/10.1083/jcb.200206023 JCB Article 893”
The ADAM metalloproteinases (2008, background): “Table 4 summarizes the known interactions of ADAMs with specific integrins, including a2b1, a4b1, a4b7, a5b1, a6b1, a6b4, a9b1, a2b1, aVb3, aVb5 (Arribas et al., 2006; Eto et al., 2002; Tomczuk et al., 2003; White et al., 2005).”