PDBsum entry 2vkx

Cell adhesion

PDB id: 2vkx

Contents

Protein chains

(+ 0 more) 199 a.a. *

Ligands

SO4 ×11

Waters ×31

* Residue conservation analysis

PDB id:

2vkx

Name:

Cell adhesion

Title:

Human ncam, fn3 domains 1 and 2, m610r mutant

Structure:

Neural cell adhesion molecule. Chain: a, b, c, d, e, f. Fragment: fn3 domains, residues 496-598,601-692. Synonym: n-cam 140, ncam-140, cd56 antigen. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: 293-ebna.

Resolution:

2.70Å R-factor: 0.223 R-free: 0.268

Authors:

F.Carafoli,J.L.Saffell,E.Hohenester

Key ref:

F.Carafoli et al. (2008). Structure of the tandem fibronectin type 3 domains of neural cell adhesion molecule. J Mol Biol, 377, 524-534. PubMed id: 18261743 DOI: 10.1016/j.jmb.2008.01.030

Date:

04-Jan-08 Release date: 26-Feb-08

Protein chains

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

Seq: 858 a.a.

Struc: 199 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2008.01.030

J Mol Biol 377:524-534 (2008)

PubMed id: 18261743

Structure of the tandem fibronectin type 3 domains of neural cell adhesion molecule.

F.Carafoli, J.L.Saffell, E.Hohenester.

ABSTRACT

Activation of the fibroblast growth factor receptor (FGFR) by neural cell adhesion molecule (NCAM) is essential for NCAM-mediated neurite outgrowth. Previous peptide studies have identified two regions in the fibronectin type 3 (FN3)-like domains of NCAM as being important for these activities. Here we report the crystal structure of the NCAM FN3 domain tandem, which reveals an acutely bent domain arrangement. Mutation of a non-conserved surface residue (M610R) led to a second crystal form showing a substantially different conformation. Thus, the FN3 domain linker is highly flexible, suggesting that it corresponds to the hinge seen in electron micrographs of NCAM. The two putative FGFR1-binding segments, one in each NCAM FN3 domain, are situated close to the domain interface. They form a contiguous patch in the more severely bent conformation but become separated upon straightening of the FN3 tandem, suggesting that conformational changes within NCAM may modulate FGFR1 activation. Surface plasmon resonance experiments demonstrated only a very weak interaction between the NCAM FN3 tandem and soluble FGFR1 proteins expressed in mammalian cells (dissociation constant >100 muM). Thus, the NCAM-FGFR1 interaction at the cell surface is likely to depend upon avidity effects due to receptor clustering.

Selected figure(s)

Figure 3.
Fig. 3. Structure of M610R mutant. (a) C^α trace of the structure of the NCAM ^1FN3–^2FN3 M610R mutant, viewed along the 3-fold non-crystallographic symmetry axis. One molecule is highlighted in yellow (^1FN3 domain) and brown (^2FN3 domains). (b) Superposition of the FN3 pairs of wild-type NCAM (cyan), NCAM M610R mutant (green) and neuroglian (magenta).^37 The structures were superimposed on the conserved β-strands of the second FN3 domain. wt indicates wild type.

Figure 4.
Fig. 4. Location of putative FGFR1 binding site. Shown are surface representations of (a) wild-type NCAM ^1FN3–^2FN3 and (b) its M610R mutant. The FRM and FGL sequences (see the text) are shown in red and yellow, respectively.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 377, 524-534) copyright 2008.

Figures were selected by an automated process.