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The CEACAM1 N-termi...
The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters
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Klaile, E (författare)
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- Vorontsova, O (författare)
- Karolinska Institutet
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Sigmundsson, K (författare)
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- Muller, MM (författare)
- Karolinska Institutet
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Singer, BB (författare)
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Ofverstedt, LG (författare)
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Svensson, S (författare)
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Skoglund, U (författare)
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- Obrink, B (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2009-11-16
- 2009
- Engelska.
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 187:4, s. 553-567
- Relaterad länk:
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http://jcb.rupress.o...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
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- art (ämneskategori)
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