PDBsum entry 3mtr

Cell adhesion

PDB id: 3mtr

Contents

Protein chains

197 a.a. *

Ligands

SO4

Waters ×340

* Residue conservation analysis

PDB id:

3mtr

Name:

Cell adhesion

Title:

Crystal structure of the ig5-fn1 tandem of human ncam

Structure:

Neural cell adhesion molecule 1. Chain: a, b. Fragment: ig5-fn1 tandem (unp residues 414 to 611). Synonym: n-cam-1, ncam-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ncam1, ncam. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.188 R-free: 0.230

Authors:

A.Lavie,D.A.Foley

Key ref:

D.A.Foley et al. (2010). Structure and mutagenesis of neural cell adhesion molecule domains: evidence for flexibility in the placement of polysialic acid attachment sites. J Biol Chem, 285, 27360-27371. PubMed id: 20573953

Date:

30-Apr-10 Release date: 23-Jun-10

Protein chains

P13591  (NCAM1_HUMAN) -  Neural cell adhesion molecule 1 from Homo sapiens

Seq: 858 a.a.

Struc: 197 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

J Biol Chem 285:27360-27371 (2010)

PubMed id: 20573953

Structure and mutagenesis of neural cell adhesion molecule domains: evidence for flexibility in the placement of polysialic acid attachment sites.

D.A.Foley, K.G.Swartzentruber, A.Lavie, K.J.Colley.

ABSTRACT

The addition of alpha2,8-polysialic acid to the N-glycans of the neural cell adhesion molecule, NCAM, is critical for brain development and plays roles in synaptic plasticity, learning and memory, neuronal regeneration, and the growth and invasiveness of cancer cells. Our previous work indicates that the polysialylation of two N-glycans located on the fifth immunoglobulin domain (Ig5) of NCAM requires the presence of specific sequences in the adjacent fibronectin type III repeat (FN1). In order to understand the relationship of these two domains, we have solved the crystal structure of the NCAM Ig5-FN1 tandem. Unexpectedly, the structure reveals that the sites of Ig5 polysialylation are on the opposite face from the FN1 residues previously found to be critical for N-glycan polysialylation, suggesting that the Ig5-FN1 domain relationship may be flexible and/or that there is flexibility in the placement of Ig5 glycosylation sites for polysialylation. To test the latter possibility, new Ig5 glycosylation sites were engineered and their polysialylation tested. We observed some flexibility in glycosylation site location for polysialylation and demonstrate that the lack of polysialylation of a glycan attached to Asn-423 may be in part related to a lack of terminal processing. The data also suggest that, while the polysialyltransferases do not require the Ig5 domain for NCAM recognition, their ability to engage with this domain is necessary for polysialylation to occur on Ig5 N-glycans.