AI Article Synopsis
- Serine/threonine phosphatases like PP1 have low substrate specificity and rely on various targeting subunits, such as ASPP proteins, for selectivity and functionality in diverse biological processes.
- Recent findings reveal that Drosophila ASPP forms a multiprotein complex with PP1 and requires this association for its proper in vivo functions.
- The crystal structure of the human ASPP2/PP1 complex shows that ASPP2 uses multiple binding motifs, including the RVxF motif and the SH3 domain, to recruit and selectively bind to different PP1 isoforms.
Article Abstract
Serine/threonine phosphatases such as PP1 lack substrate specificity and associate with a large array of targeting subunits to achieve the requisite selectivity. The tumour suppressor ASPP (apoptosis-stimulating protein of p53) proteins associate with PP1 catalytic subunits and are implicated in multiple functions from transcriptional regulation to cell junction remodelling. Here we show that Drosophila ASPP is part of a multiprotein PP1 complex and that PP1 association is necessary for several in vivo functions of Drosophila ASPP. We solve the crystal structure of the human ASPP2/PP1 complex and show that ASPP2 recruits PP1 using both its canonical RVxF motif, which binds the PP1 catalytic domain, and its SH3 domain, which engages the PP1 C-terminal tail. The ASPP2 SH3 domain can discriminate between PP1 isoforms using an acidic specificity pocket in the n-Src domain, providing an exquisite mechanism where multiple motifs are used combinatorially to tune binding affinity to PP1.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377682 | PMC |
| http://dx.doi.org/10.1038/s41467-019-08686-0 | DOI Listing |
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