22id | pdb_000022id

Structure of Chaetomium thermophilum Ufd1 UT3 domain fused with a ubiquitin C-terminal peptide

spinqualitylabelsall models 22id, resolution 2.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 22id is a 2 chain structure with sequence from Chaetomium thermophilum var. thermophilum DSM 1495. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.14Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G0RYC4_THET3 Publication Abstract from PubMed The Cdc48 ATPase (p97 or VCP in mammals) cooperates with its cofactors Ufd1 and Npl4 to extract polyubiquitinated proteins from membranes or multisubunit complexes, promoting their proteasomal degradation. A ubiquitin molecule in the chain is unfolded in an ATP-independent manner and initiates substrate translocation through the central pore of the ATPase. How ubiquitin is unfolded remains unclear. Here we demonstrate that the UT3 domain of Ufd1 specifically interacts with two K48-linked ubiquitins and unfolds one of the ubiquitins by binding its C-terminal beta-strand into a conserved hydrophobic cleft. Simultaneous binding of UT3 to two ubiquitin molecules is required to overcome the energy barrier of ubiquitin unfolding. Subsequently, the UT3-unfolded ubiquitin is captured by Npl4 and Cdc48/p97. Experiments in vitro and in cells show that unfolding-defective mutants of Ufd1 indeed compromise Cdc48/p97 function. Our results provide a reasonable explanation of how simple protein-protein interactions cause the unfolding of the remarkably stable ubiquitin. ATP-independent unfolding of ubiquitin by Ufd1 initiates Cdc48/p97-mediated substrate processing.,Wang Y, Zhang Z, He W, Wang P, Du J, Pan J, Feng S, Huang J, Ji Z Nat Struct Mol Biol. 2026 Sep 10. doi: 10.1038/s41594-026-01884-7. PMID:42722750 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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