 |
PDBsum entry 3mtr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion
|
PDB id
|
|
|
|
3mtr
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure and mutagenesis of neural cell adhesion molecule domains: evidence for flexibility in the placement of polysialic acid attachment sites.
|
|
|
Authors
|
|
D.A.Foley,
K.G.Swartzentruber,
A.Lavie,
K.J.Colley.
|
|
|
Ref.
|
|
J Biol Chem, 2010,
285,
27360-27371.
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
