scholarly journals Structural requirements for neural cell adhesion molecule-heparin interaction.

1990 ◽  
Vol 1 (8) ◽  
pp. 567-576 ◽  
Author(s):  
A A Reyes ◽  
R Akeson ◽  
L Brezina ◽  
G J Cole
Keyword(s):  
Cell Adhesion ◽  
Amino Acid ◽  
Adhesion Molecule ◽  
Synthetic Peptides ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Basic Amino Acid ◽  
Retinal Cell ◽  
Heparin Binding ◽  
Neural Cell Adhesion

Two biological domains have been identified in the amino terminal region of the neural cell adhesion molecule (NCAM): a homophilic-binding domain, responsible for NCAM-NCAM interactions, and a heparin-binding domain (HBD). It is not known whether these two domains exist as distinct structural entities in the NCAM molecule. To approach this question, we have further defined the relationship between NCAM-heparin binding and cell adhesion. A putative HBD consisting of two clusters of basic amino acid residues located close to each other in the linear amino acid sequence of NCAM has previously been identified. Synthetic peptides corresponding to this domain were shown to bind both heparin and retinal cells. Here we report the construction of NCAM cDNAs with targeted mutations in the HBD. Mouse fibroblast cells transfected with the mutant cDNAs express NCAM polypeptides with altered HBD (NCAM-102 and NCAM-104) or deleted HBD (HBD-) at levels similar to those of wild-type NCAM. Mutant NCAM polypeptides purified from transfected cell lines have substantially reduced binding to heparin and fail to promote chick retinal cell attachment. Furthermore, whereas a synthetic peptide that contains both basic amino acid clusters inhibits retinal-cell adhesion to NCAM-coated dishes, synthetic peptides in which either one of the two basic regions is altered to contain only neutral amino acids do not inhibit this adhesion. These results confirm that this region of the NCAM polypeptide does indeed mediate not only the large majority of NCAM's affinity for heparin but also a significant portion of the cell-adhesion-mediating capability of NCAM.

Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides

10.1038/13697 ◽  
1999 ◽  
Vol 17 (10) ◽  
pp. 1000-1005 ◽  
Author(s):  
Lars C.B. Rønn ◽  
Marianne Olsen ◽  
Søren Østergaard ◽  
Vladislav Kiselyov ◽  
Vladimir Berezin ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Synthetic Peptides ◽  
Combinatorial Library ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Neural Cell ◽  
Neural Cell Adhesion

scholarly journals Molecular Interactions of the Polysialytransferase Domain (PSTD) in ST8Sia IV with CMP-Sialic Acid and Polysialic Acid Required for Polysialylation of the Neural Cell Adhesion Molecule Proteins: An NMR Study

2020 ◽  
Vol 21 (5) ◽  
pp. 1590 ◽  
Author(s):  
Si-Ming Liao ◽  
Bo Lu ◽  
Xue-Hui Liu ◽  
Zhi-Long Lu ◽  
Shi-Jie Liang ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Sialic Acid ◽  
Amino Acid ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Polysialic Acid ◽  
Neural Cell ◽  
Amino Acid Residues ◽  
Neural Cell Adhesion

Polysialic acid (polySia) is an unusual glycan that posttranslational modifies neural cell adhesion molecule (NCAM) proteins in mammalian cells. The up-regulated expression of polySia-NCAM is associated with tumor progression in many metastatic human cancers and in neurocognitive processes. Two members of the ST8Sia family of α2,8-polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST) both catalyze synthesis of polySia when activated cytidine monophosphate(CMP)-Sialic acid (CMP-Sia) is translocate into the lumen of the Golgi apparatus. Two key polybasic domains in the polySTs, the polybasic region (PBR) and the polysialyltransferase domain (PSTD) areessential forpolysialylation of the NCAM proteins. However, the precise molecular details to describe the interactions required for polysialylation remain unknown. In this study, we hypothesize that PSTD interacts with both CMP-Sia and polySia to catalyze polysialylation of the NCAM proteins. To test this hypothesis, we synthesized a 35-amino acid-PSTD peptide derived from the ST8Sia IV gene sequence and used it to study its interaction with CMP-Sia, and polySia. Our results showed for the PSTD-CMP-Sia interaction, the largest chemical-shift perturbations (CSP) were in amino acid residues V251 to A254 in the short H1 helix, located near the N-terminus of PSTD. However, larger CSP values for the PSTD-polySia interaction were observed in amino acid residues R259 to T270 in the long H2 helix. These differences suggest that CMP-Sia preferentially binds to the domain between the short H1 helix and the longer H2 helix. In contrast, polySia was principally bound to the long H2 helix of PSTD. For the PSTD-polySia interaction, a significant decrease in peak intensity was observed in the 20 amino acid residues located between the N-and C-termini of the long H2 helix in PSTD, suggesting a slower motion in these residues when polySia bound to PSTD. Specific features of the interactions between PSTD-CMP-Sia, and PSTD-polySia were further confirmed by comparing their 800 MHz-derived HSQC spectra with that of PSTD-Sia, PSTD-TriSia (DP 3) and PSTD-polySia. Based on the interactions between PSTD-CMP-Sia, PSTD-polySia, PBR-NCAM and PSTD-PBR, these findingsprovide a greater understanding of the molecular mechanisms underlying polySia-NCAM polysialylation, and thus provides a new perspective for translational pharmacological applications and development by targeting the two polysialyltransferases.

scholarly journals A new member of the immunoglobulin superfamily that has a cytoplasmic region homologous to the leukocyte common antigen.

1988 ◽  
Vol 168 (5) ◽  
pp. 1523-1530 ◽  
Author(s):  
M Streuli ◽  
N X Krueger ◽  
L R Hall ◽  
S F Schlossman ◽  
H Saito
Keyword(s):  
Cell Adhesion ◽  
Amino Acid ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Neural Cell ◽  
Common Antigen ◽  
Leukocyte Common Antigen ◽  
Cytoplasmic Region ◽  
Neural Cell Adhesion

A human gene (LAR) that hybridizes to mouse leukocyte common antigen cDNA under relaxed hybridization conditions was isolated. The LAR gene is expressed in a broad range of cells, including T lymphocytes, kidney, and prostate cells. The structure of the protein encoded by the LAR gene was deduced by determining the nucleotide sequences of a 7.7-kb LAR cDNA. The putative LAR protein is composed of a 1,234 amino acid extracellular region, a 24 amino acid transmembrane segment, and a 623 amino acid cytoplasmic region. The cytoplasmic region contains two homologous domains that have extensive sequence similarity to the cytoplasmic region of the leukocyte common antigens. The NH2-terminal region of the extracellular segment of the LAR protein contains three tandem Ig-like domains and nine non-Ig-like domains. Among the known Ig-like proteins, the LAR protein has the highest degree of similarity to neural-cell adhesion molecule. The non-Ig-like domains of the LAR protein are also similar to the non-Ig-like domains of neural-cell adhesion molecule.

Expression of Neural Cell Adhesion Molecule and Polysialic Acid in Cultured Spiral Ganglion Neurons

Skull Base ◽  
2007 ◽  
Vol 17 (S 1) ◽  
Author(s):  
Kyoung Ho Park ◽  
Ki Hong Jang ◽  
Sang Yeo ◽  
Helge Rask-Andersen ◽  
Frederic Troy, II
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Polysialic Acid ◽  
Spiral Ganglion ◽  
Neural Cell ◽  
Spiral Ganglion Neurons ◽  
Neural Cell Adhesion ◽  
Ganglion Neurons
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