Identification and classification of papain-like cysteine proteinases

Ozhelvaci, Fatih; Steczkiewicz, Kamil

doi:10.1016/j.jbc.2023.104801

Cited by 11 publications

(3 citation statements)

References 290 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most notably, we identified 21 genes encoding necrosis-inducing proteins (62% core), which are known to induce plant cell death or suppress plant immune responses, but in oomycetes are known to be nontoxic (Cabral et al ., 2012; Feng et al ., 2014; Seidl and Van Den Ackerveken, 2019). Moreover, we discovered 22 genes related to glycoside hydrolase family 12 in a single cluster in the genome (45% core), known to be present in many bacteria and fungi (Zhu et al ., 2019), and 17 papain family cysteine protease genes (76% core) that are known to be involved in virulence or defence, amongst many other functions (Ozhelvaci and Steczkiewicz, 2023). When considering genes that share the same functional annotation, those that are physically clustered in the genome are much more similar to each other than genes outside clusters (68% vs 32% protein identity).…”

Section: Resultsmentioning

confidence: 99%

Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew

Skiadas,

Vidal,

Dommisse

et al. 2024

Preprint

View full text Add to dashboard Cite

Plant pathogens adapt at speeds that challenge contemporary disease management strategies like the deployment of disease resistance genes. The strong evolutionary pressure to adapt, shapes pathogens’ genomes, and comparative genomics has been instrumental in characterizing this process. With the aim to capture genomic variation at high resolution and study the processes contributing to adaptation, we here leverage and expand on an innovative, multi-genome method to construct, annotate, and analyse the first pangenome graph of an oomycete plant pathogen. We generated telomere-to-telomere genome assemblies of six genetically diverse isolates of the oomycete pathogenPeronospora effusa, the economically most important disease in cultivated spinach worldwide. The pangenome graph demonstrates thatP. effusagenomes are highly conserved, both in chromosomal structure and gene content, and revealed the continued activity of transposable elements which are directly responsible for 80% of the observed variation between the isolates. While most genes are generally conserved, pathogenicity related genes are highly variable between the isolates. Most of the variation is found in large gene clusters resulting from extensive copy-number expansion. Pangenome graph-based discovery can thus be effectively used to capture genomic variation at exceptional resolution, thereby providing a framework to study the biology and evolution of plant pathogens.Author SummaryPlant pathogens are known to evolve rapidly and overcome disease resistance of newly introduced crop varieties. This swift adaptation is visible in the genomes of these pathogens, which can be highly variable. Such genomic variation cannot be captured with contemporary comparative genomic methods that rely on a single reference genome or focus solely on protein coding genes. To overcome these limitations and compare multiple genomes in a robust and scalable method, we constructed the first pangenome graph for an oomycete filamentous plant pathogen with six telomere-to-telomere genome assemblies ofPeronospora effusa. This high-resolution pangenomic framework enabled detailed comparisons of the genomes at any level, from the nucleotide to the chromosome, and for any subset of protein-coding genes or transposable elements, to discover novel biology and potential mechanisms for the rapid evolution of this devastating pathogen.

show abstract

Section: Resultsmentioning

confidence: 99%

Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew

Skiadas,

Vidal,

Dommisse

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Due to the prevalence of a papain-like structure among the majority of DUBs families, where the catalytic cysteine residue is positioned at the N-terminal region of the core alpha helix ( Ozhelvaci and Steczkiewicz, 2023 ), they are considered homologous and consequently are grouped together in the so called CA clan according to MEROPS database ( Rawlings et al, 2018 ). Despite their mechanistic resemblances, UBL proteases usually possess a different structure characterized by a beta barrel subdomain containing the active site histidine and aspartate followed by a second subdomain consisting of a helical bundle that accommodates the catalytic cysteine ( Rawlings and Barrett, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases

Campos Alonso,

Knobeloch

2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

Proteases that cleave ubiquitin or ubiquitin-like proteins (UBLs) are critical players in maintaining the homeostasis of the organism. Concordantly, their dysregulation has been directly linked to various diseases, including cancer, neurodegeneration, developmental aberrations, cardiac disorders and inflammation. Given their potential as novel therapeutic targets, it is essential to fully understand their mechanisms of action. Traditionally, observed effects resulting from deficiencies in deubiquitinases (DUBs) and UBL proteases have often been attributed to the misregulation of substrate modification by ubiquitin or UBLs. Therefore, much research has focused on understanding the catalytic activities of these proteins. However, this view has overlooked the possibility that DUBs and UBL proteases might also have significant non-catalytic functions, which are more prevalent than previously believed and urgently require further investigation. Moreover, multiple examples have shown that either selective loss of only the protease activity or complete absence of these proteins can have different functional and physiological consequences. Furthermore, DUBs and UBL proteases have been shown to often contain domains or binding motifs that not only modulate their catalytic activity but can also mediate entirely different functions. This review aims to shed light on the non-catalytic, moonlighting functions of DUBs and UBL proteases, which extend beyond the hydrolysis of ubiquitin and UBL chains and are just beginning to emerge.

show abstract

“…Moreover, a combined approach including proteomics data and a structural analysis enabled the recognition of crucial regions and residues within cysteine cathepsins, which endow them with specific properties, thus highlighting an interplay between structural rigidity and flexibility on selectivity [30]. Very recently, a clustering of papain-like cysteine proteinases based on profile-profile mappings has shown structural conservation in addition to a well-preserved catalytic triad and oxyanion hole [31].…”

Section: Introductionmentioning

confidence: 99%

Origin and Early Diversification of the Papain Family of Cysteine Peptidases

Kordiš

Türk

2023

IJMS

View full text Add to dashboard Cite

Peptidases of the papain family play a key role in protein degradation, regulated proteolysis, and the host–pathogen arms race. Although the papain family has been the subject of many studies, knowledge about its diversity, origin, and evolution in Eukaryota, Bacteria, and Archaea is limited; thus, we aimed to address these long-standing knowledge gaps. We traced the origin and expansion of the papain family with a phylogenomic analysis, using sequence data from numerous prokaryotic and eukaryotic proteomes, transcriptomes, and genomes. We identified the full complement of the papain family in all prokaryotic and eukaryotic lineages. Analysis of the papain family provided strong evidence for its early diversification in the ancestor of eukaryotes. We found that the papain family has undergone complex and dynamic evolution through numerous gene duplications, which produced eight eukaryotic ancestral paralogous C1A lineages during eukaryogenesis. Different evolutionary forces operated on C1A peptidases, including gene duplication, horizontal gene transfer, and gene loss. This study challenges the current understanding of the origin and evolution of the papain family and provides valuable insights into their early diversification. The findings of this comprehensive study provide guidelines for future structural and functional studies of the papain family.

show abstract

Identification and classification of papain-like cysteine proteinases

Cited by 11 publications

References 290 publications

Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew

Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew

In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases

Origin and Early Diversification of the Papain Family of Cysteine Peptidases

Contact Info

Product

Resources

About