Extended Glycoprotein Structure of the Seven Domains in Human Carcinoembryonic Antigen by X-ray and Neutron Solution Scattering and an Automated Curve Fitting Procedure: Implications for Cellular Adhesion

Boehm, Mark K.; Mayans, Olga; Thornton, Jeremy; Begent, R. H. J.; Keep, P. A.; Perkins, Stephen J.

doi:10.1006/jmbi.1996.0353

Cited by 64 publications

(43 citation statements)

References 51 publications

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“…Several other studies have proposed structural motifs of CD66a family proteins (16,21,73). While our peptides of 14 amino acid residues in length contain variable numbers of residues from proposed ␤-sheet regions, our model is in general similar to other reported models.…”

Section: Discussionsupporting

confidence: 85%

Synthetic Peptides of CD66a Stimulate Neutrophil Adhesion to Endothelial Cells

Skubitz¹,

Campbell²,

Skubitz

2000

The Journal of Immunology

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Four members of the carcinoembryonic Ag family, CD66a, CD66b, CD66c, and CD66d, are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d Ab binding to the neutrophil surface triggers an activation signal that regulates the adhesive activity of CD11/CD18, resulting in an increase in neutrophil adhesion to HUVEC. To identify active sites on the CD66a Ag, molecular modeling was performed using IgG and CD4 as models, and 28 peptides of 14 aa in length were synthesized that were predicted to be present at loops and turns between β-sheets. The peptides were tested for their ability to alter neutrophil adhesion to HUVEC. Three peptides, each from the N-terminal domain, increased neutrophil adhesion to HUVEC monolayers. This increase in neutrophil adhesion caused by CD66a peptides was associated with up-regulation of CD11/CD18 and down-regulation of CD62L on the neutrophil surface. Scrambled versions of these three peptides had no effect on neutrophil adhesion to the endothelial cells. The data suggest that peptide motifs from at least three regions of the N-terminal domain of CD66a are involved in the interaction of CD66a with other ligands and can initiate signal transduction in neutrophils.

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Section: Discussionsupporting

confidence: 85%

Synthetic Peptides of CD66a Stimulate Neutrophil Adhesion to Endothelial Cells

Skubitz¹,

Campbell²,

Skubitz

2000

The Journal of Immunology

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“…The sensor response time were obtained in 1 hour. If the protein is smaller than the thickness of the SAM molecule, the mold is only a small portion will be sufficient to interact (Porter et al, 1987, Boehm et al, 1996Brayer et al, 1995). Both the hydrophobic and hydrophilic surface of CEA (Duffy, 2001;) and gold adsorption ability of proteins (Ostuni et al, 2001;Hook et al, 1998, Kaufman et al, 2007, Tang et al, 2004) with a molecular shot has to be strong.…”

Section: Electrochemical Immunosensors Developed For the Detection Ofmentioning

confidence: 99%

Biosensors for Cancer Biomarkers

Uygun¹,

Sezgintürk²

2011

Biosensors - Emerging Materials and Applications

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“…In the FnIII domain superfamily, and also in that of the structurally related nine-stranded V-type immunoglobulin fold, the GFCCh β-sheet is frequently observed to be functionally more important than the ABE β-sheet [49,50]. The former generally presents a flat surface that forms good proteinprotein contacts with appropriate surfaces.…”

Section: Homology Modelling Of the Fniii Domains In Anosmin-1mentioning

confidence: 99%

Molecular modelling and experimental studies of mutation and cell-adhesion sites in the fibronectin type III and whey acidic protein domains of human anosmin-1

Robertson

MacColl

Nash

et al. 2001

Biochemical Journal

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Anosmin-1, the gene product of the KAL gene, is implicated in the pathogenesis of X-linked Kallmann's syndrome. Anosmin-1 protein expression is restricted to the basement membrane and interstitial matrix of tissues affected in this syndrome during development. The anosmin-1 sequence indicates an N-terminal cysteine-rich domain, a whey acidic protein (WAP) domain, four fibronectin type III (FnIII) domains and a C-terminal histidine-rich region, and shows similarity with cell-adhesion molecules, such as neural cell-adhesion molecule, TAG-1 and L1. We investigated the structural and functional significance of three loss-of-function missense mutations of anosmin-1 using comparative modelling of the four FnIII and the WAP domains based on known NMR and crystal structures. Three missense mutation-encoded amino acid substitutions, N267K, E514K and F517L, were mapped to structurally defined positions on the GFCC′ β-sheet face of the first and third FnIII domains. Electrostatic maps demonstrated large basic surfaces containing clusters of conserved predicted heparan sulphate-binding residues adjacent to these mutation sites. To examine these modelling results anosmin-1 was expressed in insect cells. The incorporation of the three mutations into recombinant anosmin-1 had no effect on its secretion. The removal of two dibasic motifs that may constitute potential physiological cleavage sites for anosmin-1 had no effect on cleavage. Peptides based on the anosmin-1 sequences R254–K285 and P504–K527 were then synthesized in order to assess the effect of the three mutations on cellular adhesion, using cell lines that represented potential functional targets of anosmin-1. Peptides (10μg/ml) incorporating the N267K and E514K substitutions promoted enhanced adhesion to 13.S.1.24 rat olfactory epithelial cells and canine MDCK1 kidney epithelial cells (P<0.01) compared with the wild-type peptides. This result was attributed to the introduction of a lysine residue adjacent to the large basic surfaces. We predict that two of the three missense mutants increase the binding of anosmin-1 to an extracellular target, possibly by enhancing heparan sulphate binding, and that this critically affects the function of anosmin-1.

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Extended Glycoprotein Structure of the Seven Domains in Human Carcinoembryonic Antigen by X-ray and Neutron Solution Scattering and an Automated Curve Fitting Procedure: Implications for Cellular Adhesion

Cited by 64 publications

References 51 publications

Synthetic Peptides of CD66a Stimulate Neutrophil Adhesion to Endothelial Cells

Synthetic Peptides of CD66a Stimulate Neutrophil Adhesion to Endothelial Cells

Biosensors for Cancer Biomarkers

Molecular modelling and experimental studies of mutation and cell-adhesion sites in the fibronectin type III and whey acidic protein domains of human anosmin-1

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