Giovanna De Simone1, Alessandra di Masi1, Gian Marco Vita1, Fabio Polticelli1,2, Alessandra Pesce3, Marco Nardini4, Martino Bolognesi4,5, Chiara Ciaccio6, Massimo Coletta6, Emily Samuela Turilli7, Mauro Fasano7, Lorenzo Tognaccini8, Giulietta Smulevich8, Stefania Abbruzzetti9, Cristiano Viappiani9, Stefano Bruno10, Paolo Ascenzi1. 1. Dipartimento di Scienze, Università Roma Tre, Roma, Italy. 2. Istituto Nazionale di Fisica Nucleare, Sezione di Roma Tre, Roma, Italy. 3. Dipartimento di Fisica, Università di Genova, Genova, Italy. 4. Dipartimento di Bioscienze, Università di Milano, Milano, Italy. 5. Centro di Ricerche Pediatriche R.E. Invernizzi, Università di Milano, Milano, Italy. 6. Dipartimento di Scienze Cliniche e Medicina Traslazionale, Università di Roma Tor Vergata, Roma, Italy. 7. Dipartimento di Scienza ed Alta Tecnologia, Università dell'Insubria, Busto Arsizio, Italy. 8. Dipartimento di Chimica Ugo Schiff, Università di Firenze, Sesto Fiorentino, Italy. 9. Dipartimento di Scienze Matematiche, Fisiche e Informatiche, Università di Parma, Parma, Italy. 10. Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy.
Abstract
Aims: Nitrobindins (Nbs) are evolutionary conserved all-β-barrel heme-proteins displaying a highly solvent-exposed heme-Fe(III) atom. The physiological role(s) of Nbs is almost unknown. Here, the structural and functional properties of ferric Mycobacterium tuberculosis Nb (Mt-Nb(III)) and ferric Homo sapiens Nb (Hs-Nb(III)) have been investigated and compared with those of ferric Arabidopsis thaliana Nb (At-Nb(III), Rhodnius prolixus nitrophorins (Rp-NP(III)s), and mammalian myoglobins. Results: Data here reported demonstrate that Mt-Nb(III), At-Nb(III), and Hs-Nb(III) share with Rp-NP(III)s the capability to bind selectively nitric oxide, but display a very low reactivity, if any, toward histamine. Data obtained overexpressing Hs-Nb in human embryonic kidney 293 cells indicate that Hs-Nb localizes mainly in the cytoplasm and partially in the nucleus, thanks to a nuclear localization sequence encompassing residues Glu124-Leu154. Human Hs-Nb corresponds to the C-terminal domain of the human nuclear protein THAP4 suggesting that Nb may act as a sensor possibly modulating the THAP4 transcriptional activity residing in the N-terminal region. Finally, we provide strong evidence that both Mt-Nb(III) and Hs-Nb(III) are able to scavenge peroxynitrite and to protect free l-tyrosine against peroxynitrite-mediated nitration. Innovation: Data here reported suggest an evolutionarily conserved function of Nbs related to their role as nitric oxide sensors and components of antioxidant systems. Conclusion: Human THAP4 may act as a sensing protein that couples the heme-based Nb(III) reactivity with gene transcription. Mt-Nb(III) seems to be part of the pool of proteins required to scavenge reactive nitrogen and oxygen species produced by the host during the immunity response.
Aims: Nitrobindins (Nbs) are evolutionary conserved all-β-barrel heme-proteins displaying a highly solvent-exposed heme-Fe(III) atom. The physiological role(s) of Nbs is almost unknown. Here, the structural and functional properties of ferric Mycobacterium tuberculosis Nb (Mt-Nb(III)) and ferric Homo sapiens Nb (Hs-Nb(III)) have been investigated and compared with those of ferric Arabidopsis thaliana Nb (At-Nb(III), Rhodnius prolixus nitrophorins (Rp-NP(III)s), and mammalian myoglobins. Results: Data here reported demonstrate that Mt-Nb(III), At-Nb(III), and Hs-Nb(III) share with Rp-NP(III)s the capability to bind selectively nitric oxide, but display a very low reactivity, if any, toward histamine. Data obtained overexpressing Hs-Nb in human embryonic kidney 293 cells indicate that Hs-Nb localizes mainly in the cytoplasm and partially in the nucleus, thanks to a nuclear localization sequence encompassing residues Glu124-Leu154. Human Hs-Nb corresponds to the C-terminal domain of the human nuclear protein THAP4 suggesting that Nb may act as a sensor possibly modulating the THAP4 transcriptional activity residing in the N-terminal region. Finally, we provide strong evidence that both Mt-Nb(III) and Hs-Nb(III) are able to scavenge peroxynitrite and to protect free l-tyrosine against peroxynitrite-mediated nitration. Innovation: Data here reported suggest an evolutionarily conserved function of Nbs related to their role as nitric oxide sensors and components of antioxidant systems. Conclusion:HumanTHAP4 may act as a sensing protein that couples the heme-based Nb(III) reactivity with gene transcription. Mt-Nb(III) seems to be part of the pool of proteins required to scavenge reactive nitrogen and oxygen species produced by the host during the immunity response.
Entities:
Keywords:
Homo sapiens; Mycobacterium tuberculosis; heme; nitrobindin; peroxynitrite; reactivity; structure
Authors: Carolyn D Hurst; Guo Cheng; Fiona M Platt; Mauro A A Castro; Nour-Al-Dain S Marzouka; Pontus Eriksson; Emma V I Black; Olivia Alder; Andrew R J Lawson; Sia V Lindskrog; Julie E Burns; Sunjay Jain; Jo-An Roulson; Joanne C Brown; Jan Koster; A Gordon Robertson; Inigo Martincorena; Lars Dyrskjøt; Mattias Höglund; Margaret A Knowles Journal: Cell Rep Med Date: 2021-12-21
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