3HVQ

Crystal structure of a complex between Protein Phosphatase 1 alpha (PP1) and the PP1 binding and PDZ domains of Neurabin

Summary for 3HVQ

• Entry DOI: 10.2210/pdb3hvq/pdb
• Related: 1FJM 1S70 2FN5 2GLE 3EGG 3EGH
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, Neurabin-1, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: pp1, neurabin, serine/threonine phosphatase, post synaptic density, glutametergic receptors, 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, synaptosome, hydrolase-hydrolase regulator complex, hydrolase/hydrolase regulator
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P62136; Cytoplasm, cytoskeleton: O35867
• Total number of polymer chains: 4
• Total formula weight: 113085.40

Authors

Critton, D.A.,Ragusa, M.J.,Page, R.,Peti, W. (deposition date: 2009-06-16, release date: 2010-03-23, Last modification date: 2023-09-06)

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 (2.2 Å)