Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP

to related objects

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.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: 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)

Creator: 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

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:30 AM CEST

Data provider

This object is provided by:
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.

Show original at data provider

Associated

Munari, Francesca
Mollica, Luca
Valente, Carlo
Parolini, Francesca
Kachoie, Elham Ataie
Arrigoni, Giorgio
D'Onofrio, Mariapina
Capaldi, Stefano
Assfalg, Michael

Other Objects (12)

Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP

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

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

The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu

E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2

E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2

Tau protein binds to the P53 E3 ubiquitin ligase MDM2

Tau protein binds to the P53 E3 ubiquitin ligase MDM2

Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1

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

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

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

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

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

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

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

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

The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu

E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2

E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2

Tau protein binds to the P53 E3 ubiquitin ligase MDM2

Tau protein binds to the P53 E3 ubiquitin ligase MDM2

Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1

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

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

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

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

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

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

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

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

The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu

E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2

E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2

Tau protein binds to the P53 E3 ubiquitin ligase MDM2

Tau protein binds to the P53 E3 ubiquitin ligase MDM2

Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1

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

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

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

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

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

PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer

Cultural heritage institutions wishing to register will find more information here.

Fields marked * need to be filled in.

Username*

Please enter your username

Email*

Please enter your email address

Please do not fill this field

First name

Last name

Password*

Please enter your password

Confirm password*

Please enter the same password

I have read the terms of use and the privacy policy for the collection of personal data and accept them. *

This field is required.

I would like to subscribe to the newsletter of the Deutsche Digitale Bibliothek. See newsletter subscription info.

Account created

Your "My DDB" account has been successfully created. Before you can log in to your account, you must click the confirmation link in the message we just sent to the email address you provided.