title: The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters.
abstract: Cell adhesion molecules (CAMs) sense the extracellular microenvironment and transmit signals to the intracellular compartment. In this investigation, we addressed the mechanism of signal generation by ectodomains of single-pass transmembrane homophilic CAMs. We analyzed the structure and homophilic interactions of carcinoembryonic antigen (CEA)-related CAM 1 (CEACAM1), which regulates cell proliferation, apoptosis, motility, morphogenesis, and microbial responses. Soluble and membrane-attached CEACAM1 ectodomains were investigated by surface plasmon resonance-based biosensor analysis, molecular electron tomography, and chemical cross-linking. The CEACAM1 ectodomain, which is composed of four glycosylated immunoglobulin-like (Ig) domains, is highly flexible and participates in both antiparallel (trans) and parallel (cis) homophilic binding. Membrane-attached CEACAM1 ectodomains form microclusters in which all four Ig domains participate. Trans-binding between the N-terminal Ig domains increases formation of CEACAM1 cis-dimers and changes CEACAM1 interactions within the microclusters. These data suggest that CEACAM1 transmembrane signaling is initiated by adhesion-regulated changes of cis-interactions that are transmitted to the inner phase of the plasma membrane.
authors: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors: Esther
authors: E
authors: Klaile
authors: Olga
authors: O
authors: Vorontsova
authors: Kristmundur
authors: K
authors: Sigmundsson
authors: Mario M
authors: MM
authors: Müller
authors: Bernhard B
authors: BB
authors: Singer
authors: Lars-Göran
authors: LG
authors: Ofverstedt
authors: Stina
authors: S
authors: Svensson
authors: Ulf
authors: U
authors: Skoglund
authors: Björn
authors: B
authors: Obrink
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D011961:Receptors, Fc / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D010446:Peptide Fragments; D011961:Receptors, Fc