|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 September 2001, Vol. 98, No. 5, pp. 1469-1479
IMMUNOBIOLOGY
Homophilic adhesion of human CEACAM1 involves N-terminal domain
interactions: structural analysis of the binding site
Suzanne M. Watt,
Ana M. Teixeira,
Guang-Qian Zhou,
Regis Doyonnas,
Youyi Zhang,
Fritz Grunert,
Richard S. Blumberg,
Motomu Kuroki,
Keith M. Skubitz, and
Paul A. Bates
From the Stem Cell Laboratory, National Blood Service,
Nuffield Department of Clinical and Laboratory Sciences, and the MRC
Molecular Haematology Unit, Institute of Molecular Medicine, Oxford,
United Kingdom; Faculdade de Ciencias do Desporto e Educacao Fisica da
Universidade de Coimbra, Coimbra, Portugal; GENOVAC AG, Freiburg,
Germany; Gastroenterology Division, Brigham and Women's Hospital,
Harvard Medical School, Boston, MA; First Department of Biochemistry,
School of Medicine, Fukuoka University, Fukuoka, Japan;
Hematology, Oncology and Transplantation, University of
Minnesota Medical School, Minneapolis, MN; Biomolecular Modelling
Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
CEACAM1 on leukocytic, endothelial, and epithelial cells functions
in homophilic adhesion, tumor suppression, regulating cell adhesion and
proliferation, and in heterophilic adhesion as a receptor for
E-selectin and Neisseria meningiditis, Neisseria gonorrhoeae, Haemophilus influenzae, and murine coronaviruses. The 8 transmembrane isoforms of human CEACAM1 possess an extracellular N-terminal IgV domain, followed by variable numbers of IgC2 domains. To
establish which key amino acids contribute specifically to CEACAM1
homophilic adhesion, exposed amino acids in the N-terminal domain of a
soluble form of CEACAM1 were subjected to mutagenesis. Analyses of
mutant proteins with conformationally dependent antibodies indicated
that most mutations did not substantially affect the structural
integrity of CEACAM1. Nevertheless, decreased adhesion was observed for
the single mutants V39A or D40A (single-letter amino acid codes) in the
CC' loop and for the triple mutants located in the GFCC'C" face of the
N-terminal domain. Interestingly, whereas single mutations in R64 or
D82 that are predicted to form a salt bridge between the base of the D
and F  strands close to the critical V39 and D40 residues also
abolish adhesion, an amino acid swap (R64D and D82R), which maintains
the salt bridge was without significant effect. These studies indicate
that the CC' loop plays a crucial role in the homophilic adhesion
of CEACAM1. They further predict that specific hydrophobic amino acid
residues on the nonglycosylated GFCC'C" face of CEACAM1 N-terminal
domain are not only involved in heterophilic interactions with Opa
proteins and H influenzae, but are also critical for
protein-protein interactions between 2 CEACAM1 molecules on opposing cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Short
Adhering to the message
J. Cell Biol.,
November 16, 2009;
187(4):
445 - 445.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Klaile, O. Vorontsova, K. Sigmundsson, M. M. Muller, B. B. Singer, L.-G. Ofverstedt, S. Svensson, U. Skoglund, and B. Obrink
The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters
J. Cell Biol.,
November 16, 2009;
187(4):
553 - 567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Chen, L. Chen, S.-W. Qiao, T. Nagaishi, and R. S. Blumberg
Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits Proximal TCR Signaling by Targeting ZAP-70
J. Immunol.,
May 1, 2008;
180(9):
6085 - 6093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-J. Chen, J. Kirshner, M. A. Sherman, W. Hu, T. Nguyen, and J. E. Shively
Mutation Analysis of the Short Cytoplasmic Domain of the Cell-Cell Adhesion Molecule CEACAM1 Identifies Residues That Orchestrate Actin Binding and Lumen Formation
J. Biol. Chem.,
February 23, 2007;
282(8):
5749 - 5760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Markel, R. Seidman, N. Stern, T. Cohen-Sinai, O. Izhaki, G. Katz, M. Besser, A. J. Treves, R. S. Blumberg, R. Loewenthal, et al.
Inhibition of Human Tumor-Infiltrating Lymphocyte Effector Functions by the Homophilic Carcinoembryonic Cell Adhesion Molecule 1 Interactions
J. Immunol.,
November 1, 2006;
177(9):
6062 - 6071.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Korotkova, E. Cota, Y. Lebedin, S. Monpouet, J. Guignot, A. L. Servin, S. Matthews, and S. L. Moseley
A Subfamily of Dr Adhesins of Escherichia coli Bind Independently to Decay-accelerating Factor and the N-domain of Carcinoembryonic Antigen
J. Biol. Chem.,
September 29, 2006;
281(39):
29120 - 29130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Li, R. K.-K. Lee, Y.-L. Hsiao, and Y.-H. Chen
Demonstration of a Glycoprotein Derived From the Ceacam10 Gene in Mouse Seminal Vesicle Secretions
Biol Reprod,
September 1, 2005;
73(3):
546 - 553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Stern, G. Markel, T. I. Arnon, R. Gruda, H. Wong, S. D. Gray-Owen, and O. Mandelboim
Carcinoembryonic Antigen (CEA) Inhibits NK Killing via Interaction with CEA-Related Cell Adhesion Molecule 1
J. Immunol.,
June 1, 2005;
174(11):
6692 - 6701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Nakagaki, K. Nakagaki, and F. Taguchi
Receptor-Independent Spread of a Highly Neurotropic Murine Coronavirus JHMV Strain from Initially Infected Microglial Cells in Mixed Neural Cultures
J. Virol.,
May 15, 2005;
79(10):
6102 - 6110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Servin
Pathogenesis of Afa/Dr Diffusely Adhering Escherichia coli
Clin. Microbiol. Rev.,
April 1, 2005;
18(2):
264 - 292.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Markel, R. Gruda, H. Achdout, G. Katz, M. Nechama, R. S. Blumberg, R. Kammerer, W. Zimmermann, and O. Mandelboim
The Critical Role of Residues 43R and 44Q of Carcinoembryonic Antigen Cell Adhesion Molecules-1 in the Protection from Killing by Human NK Cells
J. Immunol.,
September 15, 2004;
173(6):
3732 - 3739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Comegys, S.-H. Lin, D. Rand, D. Britt, D. Flanagan, H. Callanan, K. Brilliant, and D. C. Hixson
Two Variable Regions in Carcinoembryonic Antigen-related Cell Adhesion Molecule1 N-terminal Domains Located in or Next to Monoclonal Antibody and Adhesion Epitopes Show Evidence of Recombination in Rat but Not in Human
J. Biol. Chem.,
August 13, 2004;
279(33):
35063 - 35078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Chen, H. Iijima, T. Nagaishi, A. Nakajima, S. Russell, R. Raychowdhury, V. Morales, C. E. Rudd, N. Utku, and R. S. Blumberg
Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 Isoforms Alternatively Inhibit and Costimulate Human T Cell Function
J. Immunol.,
March 15, 2004;
172(6):
3535 - 3543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-J. Chen and J. E. Shively
The Cell-Cell Adhesion Molecule Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 Inhibits IL-2 Production and Proliferation in Human T Cells by Association with Src Homology Protein-1 and Down-Regulates IL-2 Receptor
J. Immunol.,
March 15, 2004;
172(6):
3544 - 3552.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Markel, H. Mussaffi, K.-L. Ling, M. Salio, S. Gadola, G. Steuer, H. Blau, H. Achdout, M. de Miguel, T. Gonen-Gross, et al.
The mechanisms controlling NK cell autoreactivity in TAP2-deficient patients
Blood,
March 1, 2004;
103(5):
1770 - 1778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Iijima, M. F. Neurath, T. Nagaishi, J. N. Glickman, E. E. Nieuwenhuis, A. Nakajima, D. Chen, I. J. Fuss, N. Utku, D. N. Lewicki, et al.
Specific Regulation of T Helper Cell 1-mediated Murine Colitis by CEACAM1
J. Exp. Med.,
February 17, 2004;
199(4):
471 - 482.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Fournes, J. Farrah, M. Olson, N. Lamarche-Vane, and N. Beauchemin
Distinct Rho GTPase Activities Regulate Epithelial Cell Localization of the Adhesion Molecule CEACAM1: Involvement of the CEACAM1 Transmembrane Domain
Mol. Cell. Biol.,
October 15, 2003;
23(20):
7291 - 7304.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Nakajima, H. Iijima, M. F. Neurath, T. Nagaishi, E. E. S. Nieuwenhuis, R. Raychowdhury, J. Glickman, D. M. Blau, S. Russell, K. V. Holmes, et al.
Activation-Induced Expression of Carcinoembryonic Antigen-Cell Adhesion Molecule 1 Regulates Mouse T Lymphocyte Function
J. Immunol.,
February 1, 2002;
168(3):
1028 - 1035.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
