PDBsum entry 2fn5

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protein links
Signaling protein PDB id
Jmol PyMol
Protein chain
94 a.a. *
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Nmr structure of the neurabin pdz domain (502-594)
Structure: Neurabin-1. Chain: a. Fragment: pdz domain. Synonym: neurabin-i, neural tissue-specific f-actin binding protein i, protein phosphatase 1 regulatory subunit 9a, p180, pp1bp175. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: ppp1r9a. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Expression_system_cell_line: irl.
NMR struc: 20 models
Authors: B.Dancheck,W.Peti
Key ref: M.S.Kelker et al. (2007). Structural basis for spinophilin-neurabin receptor interaction. Biochemistry, 46, 2333-2344. PubMed id: 17279777 DOI: 10.1021/bi602341c
10-Jan-06     Release date:   09-Jan-07    
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Protein chain
Pfam   ArchSchema ?
O35867  (NEB1_RAT) -  Neurabin-1
1095 a.a.
94 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)


DOI no: 10.1021/bi602341c Biochemistry 46:2333-2344 (2007)
PubMed id: 17279777  
Structural basis for spinophilin-neurabin receptor interaction.
M.S.Kelker, B.Dancheck, T.Ju, R.P.Kessler, J.Hudak, A.C.Nairn, W.Peti.
Neurabin and spinophilin are neuronal scaffolding proteins that play important roles in the regulation of synaptic transmission through their ability to target protein phosphatase 1 (PP1) to dendritic spines where PP1 dephosphorylates and inactivates glutamate receptors. However, thus far, it is still unknown how neurabin and spinophilin themselves are targeted to these membrane receptors. Spinophilin and neurabin contain a single PDZ domain, a common protein-protein interaction recognition motif, which are 86% identical in sequence. We report the structures of both the neurabin and spinophilin PDZ domains determined using biomolecular NMR spectroscopy. These proteins form the canonical PDZ domain fold. However, despite their high degree of sequence identity, there are distinct and significant structural differences between them, especially between the peptide binding pockets. Using two-dimensional 1H-15N HSQC NMR analysis, we demonstrate that C-terminal peptide ligands derived from glutamatergic AMPA and NMDA receptors and cytosolic proteins directly and differentially bind spinophilin and neurabin PDZ domains. This peptide binding data also allowed us to classify the neurabin and spinophilin PDZ domains as the first identified neuronal hybrid class V PDZ domains, which are capable of binding both class I and II peptides. Finally, the ability to bind to glutamate receptor subunits suggests that the PDZ domains of neurabin and spinophilin are important for targeting PP1 to C-terminal phosphorylation sites in AMPA and NMDA receptor subunits.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20399103 M.Bollen, W.Peti, M.J.Ragusa, and M.Beullens (2010).
The extended PP1 toolkit: designed to create specificity.
  Trends Biochem Sci, 35, 450-458.  
20585660 P.Sánchez-Blázquez, M.Rodríguez-Muñoz, and J.Garzón (2010).
Mu-opioid receptors transiently activate the Akt-nNOS pathway to produce sustained potentiation of PKC-mediated NMDAR-CaMKII signaling.
  PLoS One, 5, e11278.  
  20717495 W.H.Lin, and D.J.Webb (2009).
Actin and Actin-Binding Proteins: Masters of Dendritic Spine Formation, Morphology, and Function.
  Open Neurosci J, 3, 54-66.  
18411314 B.Seed, and R.Xavier (2008).
Spinophilin and the immune synapse.
  J Cell Biol, 181, 181-183.  
  18028445 H.Schüler, and W.Peti (2008).
Structure-function analysis of the filamentous actin binding domain of the neuronal scaffolding protein spinophilin.
  FEBS J, 275, 59-68.  
18411422 J.Liu, J.Zhang, Y.Yang, H.Huang, W.Shen, Q.Hu, X.Wang, J.Wu, and Y.Shi (2008).
Conformational change upon ligand binding and dynamics of the PDZ domain from leukemia-associated Rho guanine nucleotide exchange factor.
  Protein Sci, 17, 1003-1014.  
17600833 T.Ju, M.J.Ragusa, J.Hudak, A.C.Nairn, and W.Peti (2007).
Structural characterization of the neurabin sterile alpha motif domain.
  Proteins, 69, 192-198.
PDB code: 2gle
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