- EMDB-43572: Human Cullin-1 in complex with CAND2 -
+
Open data
ID or keywords:
Loading...
-
Basic information
Entry
Database: EMDB / ID: EMD-43572
Title
Human Cullin-1 in complex with CAND2
Map data
Sample
Complex: CAND2-CUL1
Protein or peptide: Cullin-1
Protein or peptide: Cullin-associated NEDD8-dissociated protein 2
Keywords
Complex / LIGASE
Function / homology
Function and homology information
SCF complex assembly / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cullin-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / SCF ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / Prolactin receptor signaling / protein monoubiquitination / protein K48-linked ubiquitination ...SCF complex assembly / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cullin-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / SCF ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / Prolactin receptor signaling / protein monoubiquitination / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / intrinsic apoptotic signaling pathway / NIK-->noncanonical NF-kB signaling / SCF-beta-TrCP mediated degradation of Emi1 / TBP-class protein binding / Dectin-1 mediated noncanonical NF-kB signaling / animal organ morphogenesis / Activation of NF-kappaB in B cells / Iron uptake and transport / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of beta-catenin by the destruction complex / NOTCH1 Intracellular Domain Regulates Transcription / G1/S transition of mitotic cell cycle / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / Cyclin D associated events in G1 / Regulation of RUNX2 expression and activity / : / Regulation of PLK1 Activity at G2/M Transition / Downstream TCR signaling / Antigen processing: Ubiquitination & Proteasome degradation / Neddylation / protein-macromolecule adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / cell population proliferation / positive regulation of canonical NF-kappaB signal transduction / protein ubiquitination / ubiquitin protein ligase binding / positive regulation of DNA-templated transcription / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function
TATA-binding protein interacting (TIP20) / Cullin-associated NEDD8-dissociated protein 1/2 / TATA-binding protein interacting (TIP20) / HEAT-like repeat / Cullin protein neddylation domain / Cullin, conserved site / Cullin family signature. / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin ...TATA-binding protein interacting (TIP20) / Cullin-associated NEDD8-dissociated protein 1/2 / TATA-binding protein interacting (TIP20) / HEAT-like repeat / Cullin protein neddylation domain / Cullin, conserved site / Cullin family signature. / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / Armadillo-like helical / Armadillo-type fold / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily Similarity search - Domain/homology
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM138016
United States
Citation
Journal: Nat Commun / Year: 2025 Title: Molecular mechanisms of CAND2 in regulating SCF ubiquitin ligases. Authors: Kankan Wang / Lihong Li / Sebastian Kenny / Dailin Gan / Justin M Reitsma / Yun Zhou / Chittaranjan Das / Xing Liu / Abstract: Protein degradation orchestrated by SKP1·CUL1·F-box protein (SCF) ubiquitin ligases is a fundamental process essential for cellular and organismal function. The dynamic assembly of SCFs, ...Protein degradation orchestrated by SKP1·CUL1·F-box protein (SCF) ubiquitin ligases is a fundamental process essential for cellular and organismal function. The dynamic assembly of SCFs, facilitated by CAND1, ensures timely ubiquitination of diverse SCF target proteins. As a homolog of CAND1, CAND2 alone has been implicated in various human diseases, yet its functional mechanisms remain elusive. Here, we investigate the role of CAND2 in human cells and its distinct mode of action compared to CAND1. Using an array of quantitative assays, we demonstrate that CAND2 promotes SCF-mediated protein degradation as an F-box protein exchange factor. While CAND2 binds CUL1 with structure and affinity comparable to CAND1, it exhibits lower efficiency in exchanging F-box proteins. Kinetic measurements reveal a significantly higher K for CAND2-catalyzed SCF disassembly than CAND1, which explains the lower exchange efficiency of CAND2 and is likely due to conformations of the CAND2·SCF exchange intermediate complex being less favorable for F-box protein dissociation. Our study provides mechanistic insights into the biochemical and structural properties of CAND2, as well as its role in regulating cellular dynamics of SCFs, laying a foundation for understanding contributions of CAND2 to healthy and diseased human cells.
UniProtKB: Cullin-associated NEDD8-dissociated protein 2
-
Experimental details
-
Structure determination
Method
cryo EM
Processing
single particle reconstruction
Aggregation state
particle
-
Sample preparation
Buffer
pH: 7.4
Grid
Model: Quantifoil R1.2/1.3 / Support film - Material: CARBON / Support film - topology: HOLEY
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK II
-
Electron microscopy
Microscope
FEI TITAN KRIOS
Specialist optics
Energy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV
Image recording
Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 5333 / Average exposure time: 4.56 sec. / Average electron dose: 1.28 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi