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The receptor PTPRU is a redox sensitive pseudophosphatase.
- Source :
-
Nature communications [Nat Commun] 2020 Jun 26; Vol. 11 (1), pp. 3219. Date of Electronic Publication: 2020 Jun 26. - Publication Year :
- 2020
-
Abstract
- The receptor-linked protein tyrosine phosphatases (RPTPs) are key regulators of cell-cell communication through the control of cellular phosphotyrosine levels. Most human RPTPs possess an extracellular receptor domain and tandem intracellular phosphatase domains: comprising an active membrane proximal (D1) domain and an inactive distal (D2) pseudophosphatase domain. Here we demonstrate that PTPRU is unique amongst the RPTPs in possessing two pseudophosphatase domains. The PTPRU-D1 displays no detectable catalytic activity against a range of phosphorylated substrates and we show that this is due to multiple structural rearrangements that destabilise the active site pocket and block the catalytic cysteine. Upon oxidation, this cysteine forms an intramolecular disulphide bond with a vicinal "backdoor" cysteine, a process thought to reversibly inactivate related phosphatases. Importantly, despite the absence of catalytic activity, PTPRU binds substrates of related phosphatases strongly suggesting that this pseudophosphatase functions in tyrosine phosphorylation by competing with active phosphatases for the binding of substrates.
- Subjects :
- Amino Acid Motifs
Amino Acid Sequence
Biocatalysis
Cell Line
Disulfides metabolism
Enzyme Stability
Humans
Models, Molecular
Oxidation-Reduction
Protein Binding
Protein Domains
Receptor-Like Protein Tyrosine Phosphatases, Class 2 chemistry
Substrate Specificity
Receptor-Like Protein Tyrosine Phosphatases, Class 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32591542
- Full Text :
- https://doi.org/10.1038/s41467-020-17076-w