2G5M

Spinophilin PDZ domain

2G5M の概要

• エントリーDOI: 10.2210/pdb2g5m/pdb
• 関連するPDBエントリー: 2fn5
• NMR情報: BMRB: 6927
• 分子名称: Neurabin-2 (1 entity in total)
• 機能のキーワード: spinophilin, pdz domain, cns, synaptic transmission, protein binding
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cytoplasm, cytoskeleton: O35274
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12135.75

構造登録者

Kelker, M.S.,Peti, W. (登録日: 2006-02-23, 公開日: 2007-01-09, 最終更新日: 2024-05-29)

主引用文献

Kelker, M.S.,Dancheck, B.,Ju, T.,Kessler, R.P.,Hudak, J.,Nairn, A.C.,Peti, W.
Structural basis for spinophilin-neurabin receptor interaction.
Biochemistry, 46:2333-2344, 2007

PubMed 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.

PubMed: 17279777
DOI: 10.1021/bi602341c

実験手法

SOLUTION NMR