Culurciello, Rosanna (2022) Angiogenin-like proteins from Vertebrate Superfamily RNases: novel functional features. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Angiogenin-like proteins from Vertebrate Superfamily RNases: novel functional features
Date: 9 March 2022
Number of Pages: 120
Institution: Università degli Studi di Napoli Federico II
Department: Biologia
Dottorato: Biologia
Ciclo di dottorato: 34
Coordinatore del Corso di dottorato:
Pizzo, EliodoroUNSPECIFIED
Date: 9 March 2022
Number of Pages: 120
Keywords: RNases, angiogenin, stress granules,tRNA, SS2 RNase, auto-inhibition mechanism
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Date Deposited: 21 Mar 2022 20:00
Last Modified: 28 Feb 2024 10:23

Collection description

The vertebrate RNase Superfamily includes enzymes which, in addition to the hydrolytic activity necessary for the RNA turnover regulation, have many additional biological functions including immunomodulatory, cytotoxic, neuroprotective and stress induced properties. Except for some structural peculiarities, vertebrate RNases are quite divergent in terms of sequence identity, ranging from 20% to 100%, and these differences are the basis for the development of new and interesting structural and functional characteristics. This work is in fact based on the study of two RNases, phylogenetically very distant, which share some characteristics such as the reduced catalytic activity, the presence of three disulphide bridges, the stimulation of cell proliferation (angiogenesis), but which here have been considered for two further different aspects, which make them particularly interesting: the contribution to stress response in skin cells (human RNase 5 also known as angiogenin) and a mechanism of self-regulation of enzymatic activity (salmon RNase 2 also known as SS2). The skin is the largest organ in the human body and at the same time also the most exposed to stressful agents. To date, there was no evidence regarding the role of angiogenin (ANG) as a stress-induced RNase in the skin: in the present work it was shown for the first time that ANG is expressed in epidermal cells (HaCaT cells) and is able to modify its localization as a function of altered growth conditions. Furthermore, the treatment of the same cells with ANG and its variants (produced in recombinant form), has shown a significant increase in the stress response, suggesting a hypothetical and at the same time intriguing therapeutic potential for this protein. The second part of this work instead concerned the study of RNase 2 from Salmo salar, also known as SS2, an enzyme characterized by an atypical additional pentapeptide sequence in the C-terminal region, absent in all the other RNases of the Superfamily. This structural feature has allowed us to suppose a hypothetical mechanism of auto-inhibition of the catalytic activity. The production and characterization of two SS2 deletion mutants, as well as the analysis of the crystallographic structure of one of them, made it possible to add new information on the structural reconstruction of a functional active site, allowing to validate the hypothesis of a new mechanism of auto-inhibition, never described before in the vertebrate RNase Superfamily.


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