Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Epidermal growth factor-like (EGF) and short consensus repeat (SCR) domains are commonly found in cell surface and soluble proteins that mediate specific protein-protein recognition events. Unlike the immunoglobulin (Ig) superfamily, very little is known about the general properties of intermolecular interactions encoded by these common modules, and in particular, how specificity of binding is achieved. We have dissected the binding of CD97 (a member of the EGF-TM7 family) to the complement regulator CD55, two cell surface modular proteins that contain EGF and SCR domains, respectively. We demonstrate that the interaction is mediated solely by these domains and is characterized by a low affinity (86 microm) and rapid off-rate (at least 0.6 s(-1)). The interaction is Ca(2+) -dependent but is unaffected by glycosylation of the EGF domains. Using biotinylated multimerized peptides in cell binding assays and surface plasmon resonance, we show that a CD97-related EGF-TM7 molecule (termed EMR2), differing by only three amino acids within the EGF domains, binds CD55 with a K(D) at least an order of magnitude weaker than that of CD97. These results suggest that low affinity cell-cell interactions may be a general feature of highly expressed cell surface proteins and that specificity of SCR-EGF binding can be finely tuned by a small number of amino acid changes on the EGF module surface.

Original publication




Journal article


J Biol Chem

Publication Date





24160 - 24169


Amino Acid Sequence, Animals, Antigens, CD, Binding Sites, CD55 Antigens, CHO Cells, Calcium, Cell Line, Consensus Sequence, Cricetinae, Epidermal Growth Factor, Humans, Macromolecular Substances, Membrane Glycoproteins, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Tertiary, Receptors, G-Protein-Coupled, Repetitive Sequences, Amino Acid, Sequence Homology, Amino Acid, Surface Plasmon Resonance