Binding of Dr adhesins of <i>Escherichia coli</i> to carcinoembryonic antigen triggers receptor dissociation

Korotkova, N. N.; Yang, Yi; Trong, I. Le; Cota, Ernesto; Demeler, Borries; Marchant, Jan; Thomas, Wendy E.; Stenkamp, Ronald E.; Moseley, Steve L.; Matthews, Stephen

doi:10.1111/j.1365-2958.2007.06054.x

Cited by 56 publications

(102 citation statements)

References 38 publications

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“…Also, upon further inspection of the crystal structure that led to the suggestion of an ABED dimer, a GFCCЈCЉ dimer interface can also be found when molecules in adjacent unit cells are examined. This, along with the observation of similar GFCCЈCЉ dimers for E. coli expressed material for CEACAM5 (48) and CEACAM6 (49), supports our observation of a GFCCЈCЉ dimer for CEACAM1 in solution.…”

Section: Discussionsupporting

confidence: 75%

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)

Zhuo

Yang

Moremen

et al. 2016

Journal of Biological Chemistry

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Human carcinoembryonic antigen-related cell adhesion molecule 1 (C?/Au: EACAM1) is a cell-surface signaling molecule involved in cell adhesion, proliferation, and immune response. It is also implicated in cancer angiogenesis, progression, and metastasis. This diverse set of effects likely arises as a result of the numerous homophilic and heterophilic interactions that CEACAM1 can have with itself and other molecules. Its N-terminal Ig variable (Ig V ) domain has been suggested to be a principal player in these interactions. Previous crystal structures of the ␤-sandwich-like Ig V domain have been produced using Escherichia coli-expressed material, which lacks native glycosylation. These have led to distinctly different proposals for dimer interfaces, one involving interactions of ABED ␤-strands and the other involving GFCCC؆ ␤-strands, with the former burying one prominent glycosylation site. These structures raise ques- The human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) 2 is involved in cell adhesion, proliferation, and immune response (1, 2). It also is implicated in cancer angiogenesis, progression, and metastasis (3). More specifically, it is known that CEACAM1 is a negative-regulator of cell proliferation and is down-regulated in some tumor cells (4 -10). Yet, CEACAM1 expression is reported to protect tumor cells from killing by immune cells (11)(12)(13)(14) and it has been found that the high expression level is associated with a number of other cancers (15)(16)(17)(18)(19). It is likely that this complex set of effects arises as a result of the numerous homophilic and heterophilic interactions that CEACAM1 can have with itself and other members of the CEACAM superfamily. The N-terminal Ig variable (Ig V ) domain of CEACAM1 has been suggested to be the basis of cis and trans homo-dimer formation (20), as well as interactions with other molecules (21-24). There are crystal structures of the Ig V domain expressed in Escherichia coli, which have led to the suggestion of two distinct dimerization interfaces (24, 25). However, examination of the interfaces suggests that the extensive glycosylation found in native material would inhibit dimer formation in one of these cases. This raises questions about the actual type of dimer found in solution, with and without glycosylation. Here, we use NMR methods to examine dimer structures in solution using a non-glycosylated form expressed in E. coli, and several glycosylated variants expressed in HEK293 cells.Dimerization of cell surface molecules is a well accepted mechanism for transmitting signals from the cell surface to the interior (26). In the case of CEACAM1 it is believed that modulation of intercellular adhesion as well as transmission of signals to the cell interior involves switching between cis and trans dimerization interactions. The full-length CEACAM1 molecule is large, sharing a topology with many other cell-surface signaling molecules; the extracellular domain is composed of one Ig V -like domain and typically 3 Ig C2 -like dom...

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Section: Discussionsupporting

confidence: 75%

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)

Zhuo

Yang

Moremen

et al. 2016

Journal of Biological Chemistry

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“…Plasmid pCC90 was used as the template to introduce a stop codon at codon position 31 of DraD by site-directed mutagenesis, using a QuikChange kit as directed by the manufacturer (Stratagene). The resulting expressed peptide would include the signal peptide and only five amino acids of (33). Recombinant E. coli expressing NfaE was also constructed in our previous study (32).…”

Section: Methodsmentioning

confidence: 99%

“…However, these studies have not directly addressed the role of adhesin recognition of CEACAM receptors in E. coli internalization. It has been demonstrated that CEACAM receptors are involved in Neisseria gonorrhoeae and Neisseria meningitidis internalization by epithelial cells (4,23,40), and Dr adhesins recognize the same CEACAM domains as the neisseriae (33).…”

mentioning

confidence: 99%

Escherichia coliDraE Adhesin-Associated Bacterial Internalization by Epithelial Cells Is Promoted Independently by Decay-Accelerating Factor and Carcinoembryonic Antigen-Related Cell Adhesion Molecule Binding and Does Not Require the DraD Invasin

Korotkova¹,

Yarova-Yarovaya

Tchesnokova³

et al. 2008

Infect Immun

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The Dr family of Escherichia coli adhesins are virulence factors associated with diarrhea and urinary tract infections. Dr fimbriae are comprised of two subunits. DraE/AfaE represents the major structural, antigenic, and adhesive subunit, which recognizes decay-accelerating factor (DAF) and carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) CEA, CEACAM1, CEACAM3, and CEACAM6 as binding receptors. The DraD/AfaD subunit caps fimbriae and has been implicated in the entry of Dr-fimbriated E. coli into host cells. In this study, we demonstrate that DAF or CEACAM receptors independently promote DraEmediated internalization of E. coli by CHO cell transfectants expressing these receptors. We also found that DraE-positive recombinant bacteria adhere to and are internalized by primary human bladder epithelial cells which express DAF and CEACAMs. DraE-mediated bacterial internalization by bladder cells was inhibited by agents which disrupt lipid rafts, microtubules, and phosphatidylinositol 3-kinase (PI3K) activity. Immunofluorescence confocal microscopic examination of epithelial cells detected considerable recruitment of caveolin, ␤ 1 integrin, phosphorylated ezrin, phosphorylated PI3K, and tubulin, but not F-actin, by cell-associated bacteria. Finally, we demonstrate that the DraD subunit, previously implicated as an "invasin," is not required for ␤ 1 integrin recruitment or bacterial internalization.Urinary tract infections (UTIs) represent the most common kidney and urologic disease, affecting more than 60% of women during their lifetime (17,18). A common feature of UTI is its recurrence. About 25% of women with a first UTI have a second episode within 6 months (16). Escherichia coli is the most common etiologic agent, causing more than 80% of all UTIs. One E. coli virulence factor associated with UTI is

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“…The homodimerization of CEACAM N-terminal IgV domains, in particular those of CEACAM1 and CEACAM5, has been described previously (18,19). However, the molecular mechanisms by which CEACAMs can heterodimerize have yet to be elucidated.…”

mentioning

confidence: 97%

“…One function of CEACAMs is cell adhesion (10). CEACAMs achieve this primarily through the N-terminal IgV domain, which can dimerize either through homo-or heterophillic interactions (18)(19)(20). Dimerization of CEACAMs can be either in cis or in trans, with the latter allowing for cell-cell adhesion (21,22).…”

mentioning

confidence: 99%

Diverse oligomeric states of CEACAM IgV domains

Bonsor

Guenther

Beadenkopf

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined the crystal structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6-CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6-CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans.CEACAM | X-ray crystallography | isothermal titration calorimetry | analytical ultracentrifugation

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Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation

Cited by 56 publications

References 38 publications

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)

Escherichia coliDraE Adhesin-Associated Bacterial Internalization by Epithelial Cells Is Promoted Independently by Decay-Accelerating Factor and Carcinoembryonic Antigen-Related Cell Adhesion Molecule Binding and Does Not Require the DraD Invasin

Diverse oligomeric states of CEACAM IgV domains

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