PDBsum entry 2g5m

Protein binding

PDB id: 2g5m

Contents

Protein chain

113 a.a. *

* Residue conservation analysis

PDB id:

2g5m

Name:

Protein binding

Title:

Spinophilin pdz domain

Structure:

Neurabin-2. Chain: b. Fragment: pdz domain. Synonym: neurabin-ii, neural tissue-specific f-actin binding protein ii, protein phosphatase 1 regulatory subunit 9b, spinophilin, p130, pp1bp134. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: ppp1r9b. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

M.S.Kelker,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

Date:

23-Feb-06 Release date: 09-Jan-07

Protein chain

O35274  (NEB2_RAT) -  Neurabin-2 from Rattus norvegicus

Seq: 817 a.a.

Struc: 113 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.?

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.

ABSTRACT

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.