| Title: |
Spontaneous and chaperone-assisted metal loading in the active site of protein phosphatase-1 |
| Authors: |
Van der Hoeven, Gerd; Lemaire, Sarah; Cao, Xinyu; Claes, Zander; Karamanou, Spyridoula; Bollen, Mathieu |
| Source: |
ISSN:0014-5793 ; ISSN:1873-3468 ; Febs Letters, vol. 598 (23), (2876-2885. |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Biophysics; Cell Biology; metal incorporation; metallo-enzyme; PP1; protein phosphatase; RIPPO; CATALYTIC SUBUNIT; INHIBITOR-2; COMPLEX; PPP1R11; PPP1R2; metallo‐enzyme; Protein Phosphatase 1; Catalytic Domain; Zinc; Molecular Chaperones; Humans; Iron; Manganese; Hydrogen-Ion Concentration; 0304 Medicinal and Biomolecular Chemistry; 0601 Biochemistry and Cell Biology; 0603 Evolutionary Biology; 3101 Biochemistry and cell biology |
| Description: |
Protein phosphatase PP1 has two active-site metals (Zn2+/Fe2+) that are essential for catalysis. However, when expressed in bacteria, PP1 has two Mn2+-ions in its active site, indicating that the incorporation of Zn2+/Fe2+ depends on additional eukaryotic component(s). Here, we used purified, metal-deficient PP1 to study metal incorporation. Fe2+ was incorporated spontaneously, but Zn2+ was not. Mn2+-incorporation at physiological pH depended on the co-expression of PP1 with PPP1R2 (Inhibitor-2) or PPP1R11 (Inhibitor-3), or a pre-incubation of PP1 at pH 4. We also demonstrate that PPP1R2 and PPP1R11 are Zn2+-binding proteins but are, by themselves, not able to load PP1 with Zn2+. Our data suggest that PPP1R2 and PPP1R11 function as metal chaperones for PP1 but depend on co-chaperone(s) and/or specific modification(s) for the transfer of associated Zn2+ to PP1. ; sponsorship: This project received financial support from the Research Foundation-Flanders (FWO grant G090921N), the KU Leuven Research Fund (BOF grant C14/20/101). (Fonds Wetenschappelijk Onderzoek|G090921N, Research Foundation-Flanders (FWO)|C14/20/101, KU Leuven Research Fund (BOF grant)) ; status: Published |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/20.500.12942/764348; https://pubmed.ncbi.nlm.nih.gov/39245796 |
| DOI: |
10.1002/1873-3468.15012 |
| Availability: |
https://lirias.kuleuven.be/handle/20.500.12942/764348; https://hdl.handle.net/20.500.12942/764348; https://lirias.kuleuven.be/retrieve/eedead7c-5e81-4104-bdd3-b5880695f9fc; https://doi.org/10.1002/1873-3468.15012; https://pubmed.ncbi.nlm.nih.gov/39245796 |
| Rights: |
info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.77B27BBC |
| Database: |
BASE |