The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters

Klaile, Esther; Vorontsova, Olga; Sigmundsson, Kristmundur; Müller, Mario M.; Singer, Bernhard B.; Öfverstedt, Lars-Göran; Svensson, Stina; Skoglund, Ulf; Öbrink, Björn

The association/dissociation-binding profiles can be analyzed by a global curve-fitting procedure to get information about the underlying binding reactions and their association/ dissociation rate constants, provided that appropriate curvefitting algorithms are used. Fitting to a simple 1:1 binding model (BIAevaluation 3.1) did not give satisfying results, which of course would not be expected for a situation in which the same vasculogenesis (Gu et al., 2009) , angiogenesis (Horst et al., 2006) , cell proliferation , cell motility (Ebrahimnejad et al., 2004; Klaile et al., 2005; Müller et al., 2005) , apoptosis (Kirshner et al., 2003; , tumor growth (Leung et al., 2008) , invasion (Ebrahimnejad et al., 2004) , infection, and inflammation (Gray-Owen and Blumberg, 2006) . The primordial molecule of the CEA family, CEArelated CAM 1 (CEACAM1), is a single-pass transmembrane type I glycoprotein, which, like many immunoglobulin-like (Ig) CAMs, is expressed as differentially spliced isoforms Gray-Owen and Blumberg, 2006) . The two major isoforms, CEACAM1-4L and CEACAM1-4S, which differ only in their cytoplasmic domains, have ectodomains comprised of four glycosylated Ig domains. CEACAM1-induced cell signaling is regulated by its intercellular homophilic binding at the cell surface (Gray-Owen and Blumberg, 2006) , which is mediated by the N-terminal Ig domain (D1) in a reciprocal D1-D1 interaction (Wikström et al., 1996; Watt et al., 2001) . However, the mechanism of this adhesion-initiated signaling is still unknown.