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8OR2

CAND1-CUL1-RBX1-DCNL1

Summary for 8OR2
Entry DOI10.2210/pdb8or2/pdb
Related8OR0 8OR3 8OR4
EMDB information17115
DescriptorCullin-1, E3 ubiquitin-protein ligase RBX1, Cullin-associated NEDD8-dissociated protein 1, ... (5 entities in total)
Functional Keywordscand1, substrate receptor exchange factor, cullin-ring ligase, crl, scf, ligase, neddylation, dcnl1 co-e3, ubiquitin signaling
Biological sourceHomo sapiens (human)
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Total number of polymer chains4
Total formula weight273879.53
Authors
Shaaban, M.,Clapperton, J.A.,Ding, S.,Maeots, M.E.,Enchev, R.I. (deposition date: 2023-04-12, release date: 2023-06-28, Last modification date: 2024-07-24)
Primary citationShaaban, M.,Clapperton, J.A.,Ding, S.,Kunzelmann, S.,Maeots, M.E.,Maslen, S.L.,Skehel, J.M.,Enchev, R.I.
Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange.
Mol.Cell, 83:2332-, 2023
Cited by
PubMed Abstract: Modular SCF (SKP1-CUL1-Fbox) ubiquitin E3 ligases orchestrate multiple cellular pathways in eukaryotes. Their variable SKP1-Fbox substrate receptor (SR) modules enable regulated substrate recruitment and subsequent proteasomal degradation. CAND proteins are essential for the efficient and timely exchange of SRs. To gain structural understanding of the underlying molecular mechanism, we reconstituted a human CAND1-driven exchange reaction of substrate-bound SCF alongside its co-E3 ligase DCNL1 and visualized it by cryo-EM. We describe high-resolution structural intermediates, including a ternary CAND1-SCF complex, as well as conformational and compositional intermediates representing SR- or CAND1-dissociation. We describe in molecular detail how CAND1-induced conformational changes in CUL1/RBX1 provide an optimized DCNL1-binding site and reveal an unexpected dual role for DCNL1 in CAND1-SCF dynamics. Moreover, a partially dissociated CAND1-SCF conformation accommodates cullin neddylation, leading to CAND1 displacement. Our structural findings, together with functional biochemical assays, help formulate a detailed model for CAND-SCF regulation.
PubMed: 37339624
DOI: 10.1016/j.molcel.2023.05.034
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.2 Å)
Structure validation

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