Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
Abstract: The multi‐site ubiquitination of Tau protein found in Alzheimer's disease filaments hints at the failed attempt of neurons to remove early toxic species. The ubiquitin‐dependent degradation of Tau is regulated in vivo by the E3 ligase CHIP, a quality controller of the cell proteome dedicated to target misfolded proteins for degradation. In our study, by using site‐resolved NMR, biochemical and computational methods, we elucidate the structural determinants underlying the molecular recognition between the ligase and its intrinsically disordered substrate. We reveal a multi‐domain dynamic interaction that explains how CHIP can direct ubiquitination of Tau at multiple sites even in the absence of chaperones, including its typical partner Hsp70/Hsc70. Our findings thus provide mechanistic insight into the chaperone‐independent engagement of a disordered protein by its E3 ligase.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP ; day:18 ; month:02 ; year:2022 ; extent:1
Angewandte Chemie ; (18.02.2022) (gesamt 1)
- Urheber
-
Munari, Francesca
Mollica, Luca
Valente, Carlo
Parolini, Francesca
Kachoie, Elham Ataie
Arrigoni, Giorgio
D'Onofrio, Mariapina
Capaldi, Stefano
Assfalg, Michael
- DOI
-
10.1002/ange.202112374
- URN
-
urn:nbn:de:101:1-2022021814255249667816
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
15.08.2025, 07:30 MESZ
Datenpartner
Dieses Objekt wird bereitgestellt von:
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Munari, Francesca
- Mollica, Luca
- Valente, Carlo
- Parolini, Francesca
- Kachoie, Elham Ataie
- Arrigoni, Giorgio
- D'Onofrio, Mariapina
- Capaldi, Stefano
- Assfalg, Michael
Ähnliche Objekte (12)
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu
E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2
Tau protein binds to the P53 E3 ubiquitin ligase MDM2
Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1
Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12
SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation
The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma
NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression
PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu
E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2
Tau protein binds to the P53 E3 ubiquitin ligase MDM2
Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1
Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12
SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation
The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma
NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression
PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu
E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2
Tau protein binds to the P53 E3 ubiquitin ligase MDM2
Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1
Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12
SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation
The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma
NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression