3EGH

Crystal structure of a complex between Protein Phosphatase 1 alpha (PP1), the PP1 binding and PDZ domains of Spinophilin and the small natural molecular toxin Nodularin-R

Summary for 3EGH

• Entry DOI: 10.2210/pdb3egh/pdb
• Related: 1FJM 1S70 2G5M 3E7A 3EGG 3HVQ
• Related PRD ID: PRD_000214
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, Spinophilin, nodularin R, ... (6 entities in total)
• Functional Keywords: pp1, serine/threonine phosphatase, post synaptic density, inhibitor, carbohydrate metabolism, cell cycle, cell division, glycogen metabolism, hydrolase, iron, manganese, metal-binding, phosphoprotein, protein phosphatase, actin-binding, cell junction, cell projection, cytoskeleton, developmental protein, differentiation, neurogenesis, nucleus, synapse, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: P62136; Cytoplasm, cytoskeleton: O35274
• Total number of polymer chains: 6
• Total formula weight: 114118.92

Authors

Ragusa, M.J.,Page, R.,Peti, W. (deposition date: 2008-09-10, release date: 2010-03-23, Last modification date: 2023-11-15)

Primary citation

Ragusa, M.J.,Dancheck, B.,Critton, D.A.,Nairn, A.C.,Page, R.,Peti, W.
Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites.
Nat.Struct.Mol.Biol., 17:459-464, 2010

PubMed Abstract: The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets. PP1 associates with >or=200 regulatory proteins to form highly specific holoenzymes. These regulatory proteins target PP1 to its point of action within the cell and prime its enzymatic specificity for particular substrates. However, how they direct PP1's specificity is not understood. Here we show that spinophilin, a neuronal PP1 regulator, is entirely unstructured in its unbound form, and it binds PP1 through a folding-upon-binding mechanism in an elongated fashion, blocking one of PP1's three putative substrate binding sites without altering its active site. This mode of binding is sufficient for spinophilin to restrict PP1's activity toward a model substrate in vitro without affecting its ability to dephosphorylate its neuronal substrate, glutamate receptor 1 (GluR1). Thus, our work provides the molecular basis for the ability of spinophilin to dictate PP1 substrate specificity.

PubMed: 20305656
DOI: 10.1038/nsmb.1786

Experimental method

X-RAY DIFFRACTION (2 Å)