9qug

Structure of a UBC-Ubiquitin conjugate

spinqualitylabelsall models 9qug, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9qug is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: GOL, P4K Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UBB_HUMAN Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. Publication Abstract from PubMed UBE2O is a promiscuous ubiquitin ligase involved in cellular quality control pathways. Along with BIRC6, UBE2O is one of only two E2 enzymes that can ubiquitinate substrates in an E3-independent manner. The E2/E3 hybrid targets and multi-monoubiquitinates a multitude of orphan proteins; however, the mechanisms underlying substrate specificity and ubiquitin transfer remain poorly understood. By combining structural and biochemical approaches, we show that substrate binding by UBE2O occurs through a conserved acidic pocket formed by the N-terminal SH3-like domains and that this platform allows the recruitment of a broad range of proteins. Furthermore, we identified specific residues in the catalytic UBC domain that position ubiquitin in a closed state, confirming its confirmation, and priming it for nucleophilic attack by the incoming substrate. Importantly, the activated E2 approximately Ub conjugate is protected by a tryptophan residue, avoiding premature hydrolysis. By incorporating these findings into the UBC domain of BIRC6 our data provide the molecular basis of how specialized E2/E3 hybrid proteins function as potent ubiquitination enzymes reminiscent of the catalytic principle of RING E3 ligases. Structural basis for substrate recruitment and catalytic ubiquitin transfer by the E2/E3 hybrid enzyme UBE2O.,Kordic D, Williams TL, Deszcz L, Ehrmann JF, Arnese R, Schleiffer A, Clausen T, Meinhart A J Biol Chem. 2025 Dec 17;302(2):111073. doi: 10.1016/j.jbc.2025.111073. PMID:41419192 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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