Fertilin β (also known as ADAM2), a mammalian sperm protein that mediates gamete cell adhesion during fertilization, is a member of the ADAM protein family whose members have disintegrin domains with homology to integrin ligands found in snake venoms. Fertilin β utilizes an ECD sequence within its disintegrin domain to interact with the egg plasma membrane; the Asp is especially critical. Based on what is known about different integrin subfamilies and their ligands, we sought to characterize fertilin β binding sites on mouse eggs, focusing on integrin subfamilies that recognize short peptide sequences that include an Asp residue: the α5/α8/αv/αIIb or RGD-binding subfamily (α5β1, α8β1, αVβ1, αVβ3, αVβ5, αVβ6, αVβ8, and αIIbβ3) and the α4/α9 subfamily (α4β1, α9β1, and α4β7). We tested peptide sequences known to perturb interactions mediated by these integrins in two different assays for fertilin β binding. Peptides with the sequence MLDG, which perturb α4/α9 integrin-mediated interactions, significantly inhibit fertilin β binding to eggs, which suggests a role for a member of this integrin subfamily as a fertilin β receptor. RGD peptides, which perturb α5/α8/αv/αIIb integrin-mediated interactions, have partial inhibitory activity. The anti-α6 antibody GoH3 has little or no inhibitory activity. An antibody to the integrin-associated tetraspanin protein CD9 inhibits the binding of a multivalent presentation of fertilin β (immobilized on beads) but not soluble fertilin β, which we speculate has implications for the role of CD9 in the strengthening of fertilin β-mediated cell adhesion but not in initial ligand binding.
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1 April 2002
Analysis of the Roles of RGD-Binding Integrins, α4/α9 Integrins, α6 Integrins, and CD9 in the Interaction of the Fertilin β (ADAM2) Disintegrin Domain with the Mouse Egg Membrane
Xiaoling Zhu,
Janice P. Evans
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