6ZEI
Structure of PP1-IRSp53 S455E chimera [PP1(7-304) + linker (G/S)x9 + IRSp53(449-465)] bound to Phactr1 (516-580)
Summary for 6ZEI
| Entry DOI | 10.2210/pdb6zei/pdb |
| Descriptor | Serine/threonine-protein phosphatase PP1-alpha catalytic subunit,Brain-specific angiogenesis inhibitor 1-associated protein 2, Phosphatase and actin regulator, MANGANESE (II) ION, ... (6 entities in total) |
| Functional Keywords | pp1, phosphatase, phactr, rpel, hydrolase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 92642.18 |
| Authors | Mouilleron, S.,Treisman, R.,Fedoryshchak, R.,Lee, R.,Butler, A.M.,Prechova, M. (deposition date: 2020-06-16, release date: 2020-09-30, Last modification date: 2024-01-24) |
| Primary citation | Fedoryshchak, R.O.,Prechova, M.,Butler, A.,Lee, R.,O'Reilly, N.,Flynn, H.R.,Snijders, A.P.,Eder, N.,Ultanir, S.,Mouilleron, S.,Treisman, R. Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme. Elife, 9:-, 2020 Cited by PubMed Abstract: PPP-family phosphatases such as PP1 have little intrinsic specificity. Cofactors can target PP1 to substrates or subcellular locations, but it remains unclear how they might confer sequence-specificity on PP1. The cytoskeletal regulator Phactr1 is a neuronally enriched PP1 cofactor that is controlled by G-actin. Structural analysis showed that Phactr1 binding remodels PP1's hydrophobic groove, creating a new composite surface adjacent to the catalytic site. Using phosphoproteomics, we identified mouse fibroblast and neuronal Phactr1/PP1 substrates, which include cytoskeletal components and regulators. We determined high-resolution structures of Phactr1/PP1 bound to the dephosphorylated forms of its substrates IRSp53 and spectrin αII. Inversion of the phosphate in these holoenzyme-product complexes supports the proposed PPP-family catalytic mechanism. Substrate sequences C-terminal to the dephosphorylation site make intimate contacts with the composite Phactr1/PP1 surface, which are required for efficient dephosphorylation. Sequence specificity explains why Phactr1/PP1 exhibits orders-of-magnitude enhanced reactivity towards its substrates, compared to apo-PP1 or other PP1 holoenzymes. PubMed: 32975518DOI: 10.7554/eLife.61509 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.39 Å) |
Structure validation
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