Ribotoxins are a family of fungal ribosome-inactivating proteins displaying highly specific ribonucleolytic activity against the sarcin/ricin loop (SRL) of the larger rRNA, with α-sarcin as its best-characterized member. Their toxicity arises from the combination of this activity with their ability to cross cell membranes. The involvement of α-sarcin's loops 2 and 3 in SRL and ribosomal proteins recognition, as well as in the ribotoxin-lipid interactions involving cell penetration, has been suggested some time ago. In the work presented now different mutants have been prepared in order to study the role of these loops in their ribonucleolytic and lipid-interacting properties. The results obtained confirm that loop 3 residues Lys 111, 112, and 114 are key actors of the specific recognition of the SRL. In addition, it is also shown that Lys 114 and Tyr 48 conform a network of interactions which is essential for the catalysis. Lipid-interaction studies show that this Lys-rich region is indeed involved in the phospholipids recognition needed to cross cell membranes. Loop 2 is shown to be responsible for the conformational change which exposes the region establishing hydrophobic interactions with the membrane inner leaflets and eases penetration of ribotoxins target cells.
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http://dx.doi.org/10.1016/j.toxicon.2015.01.007 | DOI Listing |
Brief Bioinform
November 2024
Guangdong Provincial Key Laboratory of Mathematical and Neural Dynamical Systems, Great Bay University, No. 16 Daxue Rd, Songshanhu District, Dongguan, Guangdong, 523000, China.
Multimodal omics provide deeper insight into the biological processes and cellular functions, especially transcriptomics and proteomics. Computational methods have been proposed for the integration of single-cell multimodal omics of transcriptomics and proteomics. However, existing methods primarily concentrate on the alignment of different omics, overlooking the unique information inherent in each omics type.
View Article and Find Full Text PDFJ Mater Chem B
January 2025
State Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing 100190, P. R. China.
Adjuvants can enhance an immunological response, which is an important part of vaccine research. Pickering bubbles have been a mega-hit for biomedical applications, including visualization and targeted drug delivery. However, there have been no studies on Pickering bubbles as an immunological adjuvant, and the special properties and structures of Pickering bubbles may play an important role in immunization.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Introduction: Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
Platelet-derived growth factor alpha (PDGFRA) plays a significant role in various malignant tumors. PDGFRA expression boosts thyroid cancer cell proliferation and metastasis. Radiorefractory thyroid cancer is poorly differentiated, very aggressive, and resistant to radioiodine therapy.
View Article and Find Full Text PDFCureus
December 2024
General Surgery, Hayatabad Medical Complex Peshawar, Peshawar, PAK.
Objective: The study aimed to investigate the rate of conversion from laparoscopic cholecystectomy (LC) to open cholecystectomy (OC) in our population and determine the potential risk factors associated with it. Understanding these factors helps surgeons predict complex cases and plan surgeries, reducing patient risks and improving outcomes.
Methodology: A cross-sectional observational study was conducted from June 1, 2022, to May 31, 2023, at Hayatabad Medical Complex, Peshawar, on 349 patients undergoing elective LC.
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