Wheat Subtilisin/Chymotrypsin Inhibitor (WSCI) as a scaffold for novel serine protease inhibitors with a given specificity

Tedeschi, Francesca; Maro, Antimo Di; Facchiano, Angelo; Costantini, Susan; Bruni, Natalia; Capuzzi, Valeria; Ficca, Anna Grazia; Poerio, Elia

doi:10.1039/c2mb25320h

Cited by 14 publications

(10 citation statements)

References 26 publications

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“…6), consistent with analyses of other monocot BBIs [36,37]. However, previous studies have detected chymotrypsin inhibition in protein extracts from the wheat endosperm, so it is likely that this activity is performed by a distinct family of protease inhibitors, potentially members of the cereal trypsin/a-amylase inhibitor family [66,67].…”

Section: Discussionsupporting

confidence: 78%

Extensive structural variation in the Bowman-Birk inhibitor family in common wheat (Triticum aestivum L.)

Xie

Ravet

Pearce

2020

Preprint

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Background Bowman-Birk inhibitors (BBI) are a family of serine-type protease inhibitors that modulate endogenous plant proteolytic activities during different phases of development. They also inhibit exogenous proteases as a component of plant defense mechanisms, and their overexpression can confer resistance to phytophagous herbivores and multiple fungal and bacterial pathogens. Dicot BBIs are multifunctional, with a “double-headed” structure containing two separate inhibitory loops that can bind and inhibit trypsin and chymotrypsin proteases simultaneously. By contrast, monocot BBIs have a non-functional chymotrypsin inhibitory loop, although they have undergone internal duplication events giving rise to proteins with multiple BBI domains.Results We used a Hidden Markov Model (HMM) profile-based search to identify 57 BBI genes in the common wheat (Triticum aestivum L.) genome. The BBI genes are unevenly distributed, with large gene clusters in the telomeric regions of homeologous group 1 and 3 chromosomes that likely arose through a series of tandem gene duplication events. The genomes of wheat progenitors also contain contiguous clusters of BBI genes, suggesting this family underwent expansion before the domestication of common wheat. However, the BBI gene family varied in size among different cultivars, showing this family remains dynamic. Because of these expansions, the BBI gene family is larger in wheat than other monocots such as maize, rice and Brachypodium.We found BBI proteins in common wheat with intragenic homologous duplications of cysteine-rich functional domains, including one protein with four functional BBI domains. This diversification may expand the spectrum of target substrates. Expression profiling suggests that some wheat BBI proteins may be involved in regulating endogenous proteases during grain development, while others were induced in response to biotic and abiotic stresses, suggesting a role in plant defense.Conclusions Genome-wide characterization reveals that the BBI gene family in wheat is subject to a high rate of homologous tandem duplication and deletion events, giving rise to a diverse set of encoded proteins. This information will facilitate the functional characterization of individual wheat BBI genes to determine their role in wheat development and stress responses and their potential application in breeding.

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Section: Discussionsupporting

confidence: 78%

Extensive structural variation in the Bowman-Birk inhibitor family in common wheat (Triticum aestivum L.)

Xie

Ravet

Pearce

2020

Preprint

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“…A few highly represented annotations were- receptor like kinases (RLK) such as leucine rich repeat (LRR) (GO: 0005515), wall associated (GO: 0006468, GO: 0005524, GO: 0004672), and cysteine rich repeat (GO:0006468, GO:0005524, GO:0004672) RLKs, photosystem II 10 kDa protein (GO:0009654, GO:0042651, GO:0015979), disease resistant protein RPM1 (GO:0043531) in leaf; pectinesterase/ pectinesterase inhibitor 13 (GO:0005618, GO:0042545, GO:0004857, GO:0030599), Rho guanine nucleotide exchange factor 8 (GO:0005089), and Cytochrome P450 86A2 (GO:0016705, GO:0055114, GO:0020037) in spike; and Serpin Z7 (GO:0005615), rab protein (GO:0006950, GO:0009415), Defensin-like protein 1 (GO:000695), globulin 3A (GO:0045735), Low temperature-induced protein (GO:0016021), WSCI proteinase inhibitor (GO:0009611, GO:0004867) and various predicted proteins in grain. Since these genes play vital role in numerous developmental and other biological processes (Ljungberg et al, 1986; Nordin et al, 1993; Hubert et al, 2003; Okuda et al, 2009; Saito and Ueda, 2009; Gish and Clark, 2011; Francis et al, 2012; Tedeschi et al, 2012; Gu et al, 2016; Gell et al, 2017; Xing et al, 2017); the co-expressed lncRNAs might also be responsible for similar functions.…”

Section: Resultsmentioning

confidence: 99%

Survey of High Throughput RNA-Seq Data Reveals Potential Roles for lncRNAs during Development and Stress Response in Bread Wheat

et al. 2017

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Long non-coding RNAs (lncRNAs) are a family of regulatory RNAs that play essential role in the various developmental processes and stress responses. Recent advances in sequencing technology and computational methods enabled identification and characterization of lncRNAs in certain plant species, but they are less known in Triticum aestivum (bread wheat). Herein, we analyzed 52 RNA seq data (>30 billion reads) and identified 44,698 lncRNAs in T. aestivum genome, which were characterized in comparison to the coding sequences (mRNAs). Similar to the mRNAs, lncRNAs were also derived from each sub-genome and chromosome, and showed tissue developmental stage specific and differential expression, as well. The modulated expression of lncRNAs during abiotic stresses like heat, drought, and salt indicated their putative role in stress response. The co-expression of lncRNAs with vital mRNAs including various transcription factors and enzymes involved in Abscisic acid (ABA) biosynthesis, and gene ontology mapping inferred their regulatory roles in numerous biological processes. A few lncRNAs were predicted as precursor (19 lncRNAs), while some as target mimics (1,047 lncRNAs) of known miRNAs involved in various regulatory functions. The results suggested numerous functions of lncRNAs in T. aestivum, and unfolded the opportunities for functional characterization of individual lncRNA in future studies.

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“…8 ) is strongly supported by the prevention of dependence receptor loss by a Bowman-Birk inhibitor. These compounds are selective inhibitors of serine proteases [ 152 ] and are produced by many species of plant including soybeans, lentils [ 48 ], wheat [ 153 ], potatoes [ 49 , 154 ] and other sources [ 50 , 155 ]. They are highly resistant to heat and metabolism, passing largely unchanged through the gut after dietary consumption.…”

Section: Discussionmentioning

confidence: 99%

Selective depletion of tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin by environmental and endogenous serine proteases: linking diet and cancer

et al. 2016

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BackgroundThe related tumour suppressor proteins Deleted in Colorectal Cancer (DCC) and neogenin are absent or weakly expressed in many cancers, whereas their insertion into cells suppresses oncogenic behaviour. Serine proteases influence the initiation and progression of cancers although the mechanisms are unknown.MethodsThe effects of environmental (bacterial subtilisin) and endogenous mammalian (chymotrypsin) serine proteases were examined on protein expression in fresh, normal tissue and human neuroblastoma and mammary adenocarcinoma lines. Cell proliferation and migration assays (chemoattraction and wound closure) were used to examine cell function. Cells lacking DCC were transfected with an ectopic dcc plasmid.ResultsSubtilisin and chymotrypsin selectively depleted DCC and neogenin from cells at nanomolar concentrations without affecting related proteins. Cells showed reduced adherence and increased migration, but after washing they re-attached within 24 h, with recovery of protein expression. These effects are induced by chymotryptic activity as they are prevented by chymostatin and the soybean Bowman-Birk inhibitor typical of many plant protease inhibitors.Conclusions Bacillus subtilis, which secretes subtilisin is widely present in soil, the environment and the intestinal contents, while subtilisin itself is used in meat processing, animal feed probiotics and many household cleaning agents. With chymotrypsin present in chyme, blood and tissues, these proteases may contribute to cancer development by depleting DCC and neogenin. Blocking their activity by Bowman-Birk inhibitors may explain the protective effects of a plant diet. Our findings identify a potential non-genetic contribution to cancer cell behaviour which may explain both the association of processed meats and other factors with cancer incidence and the protection afforded by plant-rich diets, with significant implications for cancer prevention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2795-y) contains supplementary material, which is available to authorized users.

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Wheat Subtilisin/Chymotrypsin Inhibitor (WSCI) as a scaffold for novel serine protease inhibitors with a given specificity

Cited by 14 publications

References 26 publications

Extensive structural variation in the Bowman-Birk inhibitor family in common wheat (Triticum aestivum L.)

Extensive structural variation in the Bowman-Birk inhibitor family in common wheat (Triticum aestivum L.)

Survey of High Throughput RNA-Seq Data Reveals Potential Roles for lncRNAs during Development and Stress Response in Bread Wheat

Selective depletion of tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin by environmental and endogenous serine proteases: linking diet and cancer

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