Structural analysis of a type 1 ribosome inactivating protein reveals multiple L-asparagine-N-acetyl-D-glucosamine monosaccharide modifications: Implications for cytotoxicity

Quinoin is a type 1 ribosome-inactivating protein (RIP) we previously isolated from the seeds of pseudocereal quinoa (Chenopodium quinoa) and is known as a functional food for its beneficial effects on human health. As the presence of RIPs in edible plants could be potentially risky, here we further characterised biochemically the protein (complete amino acid sequence, homologies/differences with other RIPs and three-dimensional homology modeling) and explored its possible defensive role against pathogens. Quinoin consists of 254 amino acid residues, without cysteinyl residues. As demonstrated by similarities and homology modeling, quinoin preserves the amino acid residues of the active site (Tyr75, Tyr122, Glu177, Arg180, Phe181 and Trp206; quinoin numbering) and the RIP-fold characteristic of RIPs. The polypeptide chain of quinoin contains two N-glycosylation sites at Asn115 and Asp231, the second of which appears to be linked to sugars. Moreover, by comparative MALDI-TOF tryptic peptide mapping, two differently glycosylated forms of quinoin, named pre-quinoin-1 and pre-quinoin-2 (~0.11 mg/100 g and ~0.85 mg/100 g of seeds, respectively) were characterised. Finally, quinoin possesses: (i) strong antiviral activity, both in vitro and in vivo towards Tobacco Necrosis Virus (TNV); (ii) a growth inhibition effect on the bacterial pathogens of plants; and (iii) a slight antifungal effect against two Cryphonectria parasitica strains.

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Structural and Functional Investigation and Pharmacological Mechanism of Trichosanthin, a Type 1 Ribosome-Inactivating Protein

Toxins ◽

10.3390/toxins10080335 ◽

2018 ◽

Vol 10 (8) ◽

pp. 335 ◽

Cited By ~ 1

Author(s):

Wei-Wei Shi ◽

Kam-Bo Wong ◽

Pang-Chui Shaw

Keyword(s):

Ribosomal Rna ◽

Ribosome Inactivating Protein ◽

Pharmacological Activities ◽

Pharmacological Mechanism ◽

Functional Studies ◽

P Protein ◽

Ribosomal Stalk ◽

Functional Investigation ◽

Ribosomal P

Trichosanthin (TCS) is an RNA N-glycosidase that depurinates adenine-4324 in the conserved α-sarcin/ricin loop (α-SRL) of rat 28 S ribosomal RNA (rRNA). TCS has only one chain, and is classified as type 1 ribosome-inactivating protein (RIP). Our structural studies revealed that TCS consists of two domains, with five conserved catalytic residues Tyr70, Tyr111, Glu160, Arg163 and Phe192 at the active cleft formed between them. We also found that the structural requirements of TCS to interact with the ribosomal stalk protein P2 C-terminal tail. The structural analyses suggest TCS attacks ribosomes by first binding to the C-terminal domain of ribosomal P protein. TCS exhibits a broad spectrum of biological and pharmacological activities including anti-tumor, anti-virus, and immune regulatory activities. This review summarizes an updated knowledge in the structural and functional studies and the mechanism of its multiple pharmacological effects.

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The type-1 ribosome-inactivating protein OsRIP1 triggers caspase-independent apoptotic-like death in HeLa cells

Food and Chemical Toxicology ◽

10.1016/j.fct.2021.112590 ◽

2021 ◽

Vol 157 ◽

pp. 112590

Author(s):

Simin Chen ◽

Cláudia Figueiredo Lóssio ◽

Isabel Verbeke ◽

Joost Verduijn ◽

Bogdan Parakhonskiy ◽

...

Keyword(s):

Hela Cells ◽

Ribosome Inactivating Protein

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Hip Structural Analysis Reveals Impaired Hip Geometry in Girls With Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa647 ◽

2020 ◽

Vol 105 (12) ◽

pp. e4848-e4856

Author(s):

Taïsha V Joseph ◽

Signe Caksa ◽

Madhusmita Misra ◽

Deborah M Mitchell

Keyword(s):

Type 1 Diabetes ◽

Hip Fracture ◽

Structural Analysis ◽

Bone Age ◽

Sectional Area ◽

Hip Structural Analysis ◽

Hip Geometry ◽

Cross Sectional ◽

Skeletal Fragility

Abstract Context Among patients with type 1 diabetes (T1D), the risk of hip fracture is up to 6-fold greater than that of the general population. However, the cause of this skeletal fragility remains poorly understood. Objective To assess differences in hip geometry and imaging-based estimates of bone strength between youth with and without T1D using dual-energy x-ray absorptiometry (DXA)-based hip structural analysis. Design Cross-sectional comparison. Participants Girls ages 10 to 16 years, including n = 62 with T1D and n = 61 controls. Results The groups had similar age, bone age, pubertal stage, height, lean mass, and physical activity. Bone mineral density at the femoral neck and total hip did not differ in univariate comparisons but was lower at the femoral neck in T1D after adjusting for bone age, height, and lean mass. Subjects with T1D had significantly lower cross-sectional area, cross-sectional moment of inertia, section modulus, and cortical thickness at the narrow neck, with deficits of 5.7% to 10.3%. Cross-sectional area was also lower at the intertrochanteric region in girls with T1D. Among those T1D subjects with HbA1c greater than the cohort median of 8.5%, deficits in hip geometry and strength estimates were more pronounced. Conclusions DXA-based hip structural analysis revealed that girls with T1D have unfavorable geometry and lower estimates of bone strength at the hip, which may contribute to skeletal fragility and excess hip fracture risk in adulthood. Higher average glycemia may exacerbate effects of T1D on hip geometry.

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