ArticleBMC structural biology2017
Prokaryotic ubiquitin-like protein remains intrinsically disordered when covalently attached to proteasomal target proteins.
Article in BMC structural biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Mapping the structural heterogeneity of Pup ligase PafA using H/D exchange mass spectrometry.The Journal of biological chemistry · 2025Article
- Identification of a depupylation regulator for an essential enzyme inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb).Pharmaceuticals (Basel, Switzerland) · 2024Review
- Electrostatic interactions guide substrate recognition of the prokaryotic ubiquitin-like protein ligase PafA.Nature communications · 2023Article
- Backbone NMR resonance assignment of the intrinsically disordered UBact protein from Nitrospira nitrosa.Biomolecular NMR assignments · 2022Article
- Structures of prokaryotic ubiquitin-like protein Pup in complex with depupylase Dop reveal the mechanism of catalytic phosphate formation.Nature communications · 2021Article
- Survival in Hostile Conditions: Pupylation and the Proteasome in Actinobacterial Stress Response Pathways.Frontiers in molecular biosciences · 2021Review
- Applications of Bacterial Degrons and Degraders - Toward Targeted Protein Degradation in Bacteria.Frontiers in molecular biosciences · 2021Review
- Unraveling proteasome engagement.Nature chemical biology · 2020Article
- New technologies to analyse protein function: an intrinsic disorder perspective.F1000Research · 2020Review
- Pupylated proteins are subject to broad proteasomal degradation specificity and differential depupylation.PloS one · 2019Article
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Authors and funding
6 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe post-translational modification pathway referred to as pupylation marks proteins for proteasomal degradation in Mycobacterium tuberculosis and other actinobacteria by covalently attaching the small protein Pup (prokaryotic ubiquitin-like protein) to target lysine residues. In contrast to the functionally analogous eukaryotic ubiquitin, Pup is intrinsically disordered in its free form. Its unfolded state allows Pup to adopt different structures upon interaction with different binding partners like the Pup ligase PafA and the proteasomal ATPase Mpa. While the disordered behavior of free Pup has been well characterized, it remained unknown whether Pup adopts a distinct structure when attached to a substrate.
resultsUsing a combination of NMR experiments and biochemical analysis we demonstrate that Pup remains unstructured when ligated to two well-established pupylation substrates targeted for proteasomal degradation in Mycobacterium tuberculosis, malonyl transacylase (FabD) and ketopantoyl hydroxylmethyltransferase (PanB). Isotopically labeled Pup was linked to FabD and PanB by in vitro pupylation to generate homogeneously pupylated substrates suitable for NMR analysis. The single target lysine of PanB was identified by a combination of mass spectroscopy and mutational analysis. Chemical shift comparison between Pup in its free form and ligated to substrate reveals intrinsic disorder of Pup in the conjugate.
conclusionWhen linked to the proteasomal substrates FabD and PanB, Pup is unstructured and retains the ability to interact with its different binding partners. This suggests that it is not the conformation of Pup attached to these two substrates which determines their delivery to the proteasome, but the availability of the degradation complex and the depupylase.
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