Enforcing the positive charge of N-termini enhances membrane interaction and antitumor activity of bovine seminal ribonuclease(772 views) D'Errico G, Ercole C, Lista M, Pizzo E, Falanga A, Galdiero S, Spadaccini R, Picone D
Dipartimento di Chimica Paolo Corradini, Università Degli Studi di Napoli Federico II, Via Cintia, 80126 Napoli, Italy
CSGI, Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi A Grande Interfase, Italy
Dipartimento di Biologia Strutturale e Funzionale, Università Degli Studi di Napoli Federico II, Via Cintia, 80126 Napoli, Italy
Dipartimento di Scienze Biologiche, Università Degli Studi di Napoli Federico II, Via Mezzocannone 16, 80134 Napoli, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Napoli, Italy
References: Not available.
Enforcing the positive charge of N-termini enhances membrane interaction and antitumor activity of bovine seminal ribonuclease
Binding to cell membrane, followed by translocation into the cytosol and RNA degradation, is a necessary requirement to convert a ribonuclease into a cytotoxin for malignant tumor cells. In this paper, we investigate the membrane binding attitude of bovine seminal ribonuclease (BS-RNase) and its variant G38K-BS-RNase, bearing an enforced cluster of positive charges at the N-termini surface. By using a combination of biophysical techniques, including CD. SPR and ESR, we find for the two proteins a common, two-step mechanism of interaction with synthetic liposomes, an initial binding to the bilayer surface, driven by electrostatic interactions, followed by a shallow penetration in the lipid core. Protein binding effectively perturbs lipid packing and dynamics. Remarkably, the higher G38K-BS-RNase membrane interacting capability well correlates with its increased cytotoxicity for tumor cells. Overall, these studies shed light on the mechanism of membrane binding and perturbation, proving definitely the importance of electrostatic interactions in the cytotoxic activity of BS-RNase, and provide a rational basis to design proteins with anticancer potential. (C) 2011 Elsevier B.V. All rights reserved.
Enforcing the positive charge of N-termini enhances membrane interaction and antitumor activity of bovine seminal ribonuclease
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Enforcing the positive charge of N-termini enhances membrane interaction and antitumor activity of bovine seminal ribonuclease
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(418 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote