Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	E3 ligase autoinhibition by C-degron mimicry maintains C-degron substrate fidelity.
Journal, issue, pages	Mol Cell, Vol. 83, Issue 5, Page 770-786.e9, Year 2023
Publish date	Mar 2, 2023
Authors	Daniel C Scott / Moeko T King / Kheewoong Baek / Clifford T Gee / Ravi Kalathur / Jerry Li / Nicholas Purser / Amanda Nourse / Sergio C Chai / Sivaraja Vaithiyalingam / Taosheng Chen / Richard E Lee / Stephen J Elledge / Gary Kleiger / Brenda A Schulman /
PubMed Abstract	E3 ligase recruitment of proteins containing terminal destabilizing motifs (degrons) is emerging as a major form of regulation. How those E3s discriminate bona fide substrates from other proteins ...E3 ligase recruitment of proteins containing terminal destabilizing motifs (degrons) is emerging as a major form of regulation. How those E3s discriminate bona fide substrates from other proteins with terminal degron-like sequences remains unclear. Here, we report that human KLHDC2, a CRL2 substrate receptor targeting C-terminal Gly-Gly degrons, is regulated through interconversion between two assemblies. In the self-inactivated homotetramer, KLHDC2's C-terminal Gly-Ser motif mimics a degron and engages the substrate-binding domain of another protomer. True substrates capture the monomeric CRL2, driving E3 activation by neddylation and subsequent substrate ubiquitylation. Non-substrates such as NEDD8 bind KLHDC2 with high affinity, but its slow on rate prevents productive association with CRL2. Without substrate, neddylated CRL2 assemblies are deactivated via distinct mechanisms: the monomer by deneddylation and the tetramer by auto-ubiquitylation. Thus, substrate specificity is amplified by KLHDC2 self-assembly acting like a molecular timer, where only bona fide substrates may bind before E3 ligase inactivation.
External links	Mol Cell / PubMed:36805027 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.37 - 8.2 Å
Structure data	EMDB-16370: Structure of CUL2-KLHDC2 E3 ligase autoinhibited by C-degron mimicry Method: EM (single particle) / Resolution: 8.2 Å PDB-8ebl: Structure of KLHDC2 substrate binding domain bound to C-degron from EPHB2 Method: X-RAY DIFFRACTION / Resolution: 1.37 Å PDB-8ebm: Structure of KLHDC2 substrate binding domain bound to KLHDC2's C-degron mimic Method: X-RAY DIFFRACTION / Resolution: 1.58 Å PDB-8ebn: Structure of KLHDC2-EloB/C tetrameric assembly Method: X-RAY DIFFRACTION / Resolution: 2.6 Å
Chemicals	ChemComp-HOH: WATER
Source	homo sapiens (human)
Keywords	LIGASE / E3 ligase