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PDBsum entry 1lwr
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Cell adhesion PDB id
1lwr

 

 

 

 

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Contents
Protein chain
96 a.a. *
* Residue conservation analysis
PDB id:
1lwr
Name: Cell adhesion
Title: Solution structure of the ncam fibronectin type iii module 2
Structure: Neural cell adhesion molecule 1, 140 kda isoform. Chain: a. Synonym: ncam. Ncam polypeptide. N-cam 140. Ncam-140. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: ncam1. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
NMR struc: 30 models
Authors: V.V.Kiselyov,G.Skladchikova,A.M.Hinsby,P.H.Jensen,N.Kulahin, N.Pedersen,V.Tsetlin,F.M.Poulsen,V.Berezin,E.Bock
Key ref:
V.V.Kiselyov et al. (2003). Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure, 11, 691-701. PubMed id: 12791257 DOI: 10.1016/S0969-2126(03)00096-0
Date:
03-Jun-02     Release date:   03-Jun-03    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P13596  (NCAM1_RAT) -  Neural cell adhesion molecule 1 from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		858 a.a.
96 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
DOI no: 10.1016/S0969-2126(03)00096-0 Structure 11:691-701 (2003)
PubMed id: 12791257  
 
 
Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP.
V.V.Kiselyov, G.Skladchikova, A.M.Hinsby, P.H.Jensen, N.Kulahin, V.Soroka, N.Pedersen, V.Tsetlin, F.M.Poulsen, V.Berezin, E.Bock.
 
  ABSTRACT  
 
The neural cell adhesion molecule (NCAM) promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). NCAM also has a little-understood ATPase activity. We here demonstrate for the first modules 1 and 2) and FGFR1 (Ig modules 2 and 3) by surface plasmon resonance (SPR) analysis. The structure of the NCAM F3 module 2 was determined by NMR and the module was shown by NMR to interact with the FGFR1 Ig module 3 and ATP. The NCAM sites binding to FGFR and ATP were found to overlap and ATP was shown by SPR to inhibit the NCAM-FGFR binding, indicating that ATP probably regulates the NCAM-FGFR interaction. Furthermore, we demonstrate that the NCAM module was able to induce activation (phosphorylation) of FGFR and to stimulate neurite outgrowth. In contrast, ATP inhibited neurite outgrowth induced by the module.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structure of the NCAM F3 Module 2(A) Stereo view of an overlay of the backbone atoms of 30 superimposed structures.(B) Ribbon representation of the structure.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 691-701) copyright 2003.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19921700 R.Bisaz, M.Schachner, and C.Sandi (2011).
Causal evidence for the involvement of the neural cell adhesion molecule, NCAM, in chronic stress-induced cognitive impairments.
  Hippocampus, 21, 56-71.  
21346732 U.Cavallaro, and E.Dejana (2011).
Adhesion molecule signalling: not always a sticky business.
  Nat Rev Mol Cell Biol, 12, 189-197.  
20564212 C.R.Degnin, M.B.Laederich, and W.A.Horton (2010).
FGFs in endochondral skeletal development.
  J Cell Biochem, 110, 1046-1057.  
19627396 D.Leali, R.Bianchi, A.Bugatti, S.Nicoli, S.Mitola, L.Ragona, S.Tomaselli, G.Gallo, S.Catello, V.Rivieccio, L.Zetta, and M.Presta (2010).
Fibroblast growth factor 2-antagonist activity of a long-pentraxin 3-derived anti-angiogenic pentapeptide.
  J Cell Mol Med, 14, 2109-2121.  
18468731 E.J.Downer, T.R.Cowley, A.Lyons, K.H.Mills, V.Berezin, E.Bock, and M.A.Lynch (2010).
A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL.
  Neurobiol Aging, 31, 118-128.  
20640153 S.Li, E.Bock, and V.Berezin (2010).
Neuritogenic and neuroprotective properties of Peptide agonists of the fibroblast growth factor receptor.
  Int J Mol Sci, 11, 2291-2305.  
20874775 V.Murcia-Belmonte, P.F.Esteban, D.García-González, and F.De Castro (2010).
Biochemical dissection of Anosmin-1 interaction with FGFR1 and components of the extracellular matrix.
  J Neurochem, 115, 1256-1265.  
21244325 Y.Chen, and B.L.Tang (2010).
Unique intracellular trafficking processes associated with neural cell adhesion molecule and its intracellular signaling.
  Cell Commun Adhes, 17, 69-74.  
19454531 A.Mehanna, B.Mishra, N.Kurschat, C.Schulze, S.Bian, G.Loers, A.Irintchev, and M.Schachner (2009).
Polysialic acid glycomimetics promote myelination and functional recovery after peripheral nerve injury in mice.
  Brain, 132, 1449-1462.  
20038681 C.Francavilla, P.Cattaneo, V.Berezin, E.Bock, D.Ami, A.de Marco, G.Christofori, and U.Cavallaro (2009).
The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking.
  J Cell Biol, 187, 1101-1116.  
19457161 E.J.Downer, T.R.Cowley, F.Cox, F.O.Maher, V.Berezin, E.Bock, and M.A.Lynch (2009).
A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation.
  J Neurochem, 109, 1516-1525.  
19210540 H.Umemori (2009).
Weaving the neuronal net with target-derived fibroblast growth factors.
  Dev Growth Differ, 51, 263-270.  
19666467 K.Kirschbaum, M.Kriebel, E.U.Kranz, O.Pötz, and H.Volkmer (2009).
Analysis of non-canonical fibroblast growth factor receptor 1 (FGFR1) interaction reveals regulatory and activating domains of neurofascin.
  J Biol Chem, 284, 28533-28542.  
19053057 M.R.Bryant, C.B.Marta, F.S.Kim, and R.Bansal (2009).
Phosphorylation and lipid raft association of fibroblast growth factor receptor-2 in oligodendrocytes.
  Glia, 57, 935-946.  
19185025 N.Kulahin, S.Li, V.Kiselyov, E.Bock, and V.Berezin (2009).
Identification of neural cell adhesion molecule L1-derived neuritogenic ligands of the fibroblast growth factor receptor.
  J Neurosci Res, 87, 1806-1812.  
19634127 S.Li, C.Christensen, L.B.Køhler, V.V.Kiselyov, V.Berezin, and E.Bock (2009).
Agonists of fibroblast growth factor receptor induce neurite outgrowth and survival of cerebellar granule neurons.
  Dev Neurobiol, 69, 837-854.  
18985724 U.M.Polanska, D.G.Fernig, and T.Kinnunen (2009).
Extracellular interactome of the FGF receptor-ligand system: Complexities and the relative simplicity of the worm.
  Dev Dyn, 238, 277-293.  
19696444 Y.Hu, S.E.Guimond, P.Travers, S.Cadman, E.Hohenester, J.E.Turnbull, S.H.Kim, and P.M.Bouloux (2009).
Novel mechanisms of fibroblast growth factor receptor 1 regulation by extracellular matrix protein anosmin-1.
  J Biol Chem, 284, 29905-29920.  
19141676 Y.Mao, and M.Freeman (2009).
Fasciclin 2, the Drosophila orthologue of neural cell-adhesion molecule, inhibits EGF receptor signalling.
  Development, 136, 473-481.  
18973581 A.Aonurm-Helm, M.Jurgenson, T.Zharkovsky, K.Sonn, V.Berezin, E.Bock, and A.Zharkovsky (2008).
Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL.
  Eur J Neurosci, 28, 1618-1628.  
18593816 A.Kochoyan, F.M.Poulsen, V.Berezin, E.Bock, and V.V.Kiselyov (2008).
Structural basis for the activation of FGFR by NCAM.
  Protein Sci, 17, 1698-1705.  
18586016 C.A.Turner, E.L.Gula, L.P.Taylor, S.J.Watson, and H.Akil (2008).
Antidepressant-like effects of intracerebroventricular FGF2 in rats.
  Brain Res, 1224, 63-68.  
17975827 D.K.Ditlevsen, G.K.Povlsen, V.Berezin, and E.Bock (2008).
NCAM-induced intracellular signaling revisited.
  J Neurosci Res, 86, 727-743.  
18195593 E.Borcel, L.Pérez-Alvarez, A.I.Herrero, T.Brionne, E.Varea, V.Berezin, E.Bock, C.Sandi, and C.Venero (2008).
Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule.
  Behav Pharmacol, 19, 41-49.  
18261743 F.Carafoli, J.L.Saffell, and E.Hohenester (2008).
Structure of the tandem fibronectin type 3 domains of neural cell adhesion molecule.
  J Mol Biol, 377, 524-534.
PDB codes: 2vkw 2vkx
18368482 J.Jacobsen, V.Kiselyov, E.Bock, and V.Berezin (2008).
A peptide motif from the second fibronectin module of the neural cell adhesion molecule, NCAM, NLIKQDDGGSPIRHY, is a binding site for the FGF receptor.
  Neurochem Res, 33, 2532-2539.  
18289872 L.H.Brennaman, and P.F.Maness (2008).
Developmental regulation of GABAergic interneuron branching and synaptic development in the prefrontal cortex by soluble neural cell adhesion molecule.
  Mol Cell Neurosci, 37, 781-793.  
19305742 D.Kiryushko, E.Bock, and V.Berezin (2007).
Pharmacology of cell adhesion molecules of the nervous system.
  Curr Neuropharmacol, 5, 253-267.  
17256769 D.O.Cicero, G.M.Contessa, T.A.Pertinhez, M.Gallo, A.M.Katsuyama, M.Paci, C.S.Farah, and A.Spisni (2007).
Solution structure of ApaG from Xanthomonas axonopodis pv. citri reveals a fibronectin-3 fold.
  Proteins, 67, 490-500.
PDB code: 2f1e
17658613 E.Gascon, L.Vutskits, and J.Z.Kiss (2007).
Polysialic acid-neural cell adhesion molecule in brain plasticity: from synapses to integration of new neurons.
  Brain Res Rev, 56, 101-118.  
17294447 M.Jarahian, C.Watzl, Y.Issa, P.Altevogt, and F.Momburg (2007).
Blockade of natural killer cell-mediated lysis by NCAM140 expressed on tumor cells.
  Int J Cancer, 120, 2625-2634.  
17375985 R.Anand, M.Seiberling, T.Kamtchoua, and R.Pokorny (2007).
Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers.
  Clin Pharmacokinet, 46, 351-358.  
17854387 R.K.Hansen, C.Christensen, I.Korshunova, M.Kriebel, N.Burkarth, V.V.Kiselyov, M.Olsen, S.Ostergaard, A.Holm, H.Volkmer, P.S.Walmod, V.Berezin, and E.Bock (2007).
Identification of NCAM-binding peptides promoting neurite outgrowth via a heterotrimeric G-protein-coupled pathway.
  J Neurochem, 103, 1396-1407.  
16718462 L.G.Petersen, J.Størling, P.Heding, S.Li, V.Berezin, J.Saldeen, N.Billestrup, E.Bock, and T.Mandrup-Poulsen (2006).
IL-1beta-induced pro-apoptotic signalling is facilitated by NCAM/FGF receptor signalling and inhibited by the C3d ligand in the INS-1E rat beta cell line.
  Diabetologia, 49, 1864-1875.  
16932275 P.S.Tsai, and J.C.Gill (2006).
Mechanisms of disease: Insights into X-linked and autosomal-dominant Kallmann syndrome.
  Nat Clin Pract Endocrinol Metab, 2, 160-171.  
17008716 V.V.Kiselyov, A.Kochoyan, F.M.Poulsen, E.Bock, and V.Berezin (2006).
Elucidation of the mechanism of the regulatory function of the Ig1 module of the fibroblast growth factor receptor 1.
  Protein Sci, 15, 2318-2322.  
16731982 V.V.Kiselyov, E.Bock, V.Berezin, and F.M.Poulsen (2006).
NMR structure of the first Ig module of mouse FGFR1.
  Protein Sci, 15, 1512-1515.
PDB code: 2ckn
16135080 A.A.Anderson, C.E.Kendal, M.Garcia-Maya, A.V.Kenny, S.A.Morris-Triggs, T.Wu, R.Reynolds, E.Hohenester, and J.L.Saffell (2005).
A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival.
  J Neurochem, 95, 570-583.  
16245069 A.S.Shingo, and S.Kito (2005).
Effects of nicotine on neurogenesis and plasticity of hippocampal neurons.
  J Neural Transm, 112, 1475-1478.  
16197499 G.G.Skibo, I.V.Lushnikova, K.Y.Voronin, O.Dmitrieva, T.Novikova, B.Klementiev, E.Vaudano, V.A.Berezin, and E.Bock (2005).
A synthetic NCAM-derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo.
  Eur J Neurosci, 22, 1589-1596.  
15884014 M.V.Hübschmann, G.Skladchikova, E.Bock, and V.Berezin (2005).
Neural cell adhesion molecule function is regulated by metalloproteinase-mediated ectodomain release.
  J Neurosci Res, 80, 826-837.  
16181411 N.Kulahin, O.Rudenko, V.Kiselyov, F.M.Poulsen, V.Berezin, and E.Bock (2005).
Modulation of the homophilic interaction between the first and second Ig modules of neural cell adhesion molecule by heparin.
  J Neurochem, 95, 46-55.  
16027151 S.S.Mendiratta, N.Sekulic, A.Lavie, and K.J.Colley (2005).
Specific amino acids in the first fibronectin type III repeat of the neural cell adhesion molecule play a role in its recognition and polysialylation by the polysialyltransferase ST8Sia IV/PST.
  J Biol Chem, 280, 32340-32348.  
16262654 T.Yang, W.Yin, V.D.Derevyanny, L.A.Moore, and F.M.Longo (2005).
Identification of an ectodomain within the LAR protein tyrosine phosphatase receptor that binds homophilically and activates signalling pathways promoting neurite outgrowth.
  Eur J Neurosci, 22, 2159-2170.  
16045455 V.V.Kiselyov, V.Soroka, V.Berezin, and E.Bock (2005).
Structural biology of NCAM homophilic binding and activation of FGFR.
  J Neurochem, 94, 1169-1179.  
15381695 A.R.Atkins, W.J.Gallin, G.C.Owens, G.M.Edelman, and B.A.Cunningham (2004).
Neural cell adhesion molecule (N-CAM) homophilic binding mediated by the two N-terminal Ig domains is influenced by intramolecular domain-domain interactions.
  J Biol Chem, 279, 49633-49643.  
15365636 C.Dodé, and J.P.Hardelin (2004).
Kallmann syndrome: fibroblast growth factor signaling insufficiency?
  J Mol Med, 82, 725-734.  
15550947 C.Sandi (2004).
Stress, cognitive impairment and cell adhesion molecules.
  Nat Rev Neurosci, 5, 917-930.  
15153429 D.Kiryushko, V.Berezin, and E.Bock (2004).
Regulators of neurite outgrowth: role of cell adhesion molecules.
  Ann N Y Acad Sci, 1014, 140-154.  
15134634 H.E.Bülow, T.Boulin, and O.Hobert (2004).
Differential functions of the C. elegans FGF receptor in axon outgrowth and maintenance of axon position.
  Neuron, 42, 367-374.  
  14964308 U.Cavallaro, and G.Christofori (2004).
Cell adhesion and signalling by cadherins and Ig-CAMs in cancer.
  Nat Rev Cancer, 4, 118-132.  
14580339 M.V.Poyurovsky, X.Jacq, C.Ma, O.Karni-Schmidt, P.J.Parker, M.Chalfie, J.L.Manley, and C.Prives (2003).
Nucleotide binding by the Mdm2 RING domain facilitates Arf-independent Mdm2 nucleolar localization.
  Mol Cell, 12, 875-887.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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