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Open AccessArticle

Dynamical Behavior of the Human Ferroportin Homologue from Bdellovibrio bacteriovorus: Insight into the Ligand Recognition Mechanism

1
Department of Sciences, Roma Tre University, 00146 Rome, Italy
2
Department of Biochemical Sciences, Sapienza University of Roma, 00185 Rome, Italy
3
Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy
4
Department Biosciences and Territory, University of Molise, 86090 Pesche, Italy
5
National Institute of Nuclear Physics, Roma Tre Section, 00146 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6785; https://doi.org/10.3390/ijms21186785
Received: 14 July 2020 / Revised: 14 September 2020 / Accepted: 15 September 2020 / Published: 16 September 2020
Members of the major facilitator superfamily of transporters (MFS) play an essential role in many physiological processes such as development, neurotransmission, and signaling. Aberrant functions of MFS proteins are associated with several diseases, including cancer, schizophrenia, epilepsy, amyotrophic lateral sclerosis and Alzheimer’s disease. MFS transporters are also involved in multidrug resistance in bacteria and fungi. The structures of most MFS members, especially those of members with significant physiological relevance, are yet to be solved. The lack of structural and functional information impedes our detailed understanding, and thus the pharmacological targeting, of these transporters. To improve our knowledge on the mechanistic principles governing the function of MSF members, molecular dynamics (MD) simulations were performed on the inward-facing and outward-facing crystal structures of the human ferroportin homologue from the Gram-negative bacterium Bdellovibrio bacteriovorus (BdFpn). Several simulations with an excess of iron ions were also performed to explore the relationship between the protein’s dynamics and the ligand recognition mechanism. The results reinforce the existence of the alternating-access mechanism already described for other MFS members. In addition, the reorganization of salt bridges, some of which are conserved in several MFS members, appears to be a key molecular event facilitating the conformational change of the transporter. View Full-Text
Keywords: ferroportin; Bdellovibrio bacteriovorus; major facilitator superfamily; molecular dynamics; iron transporter ferroportin; Bdellovibrio bacteriovorus; major facilitator superfamily; molecular dynamics; iron transporter
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Tortosa, V.; Bonaccorsi di Patti, M.C.; Iacovelli, F.; Pasquadibisceglie, A.; Falconi, M.; Musci, G.; Polticelli, F. Dynamical Behavior of the Human Ferroportin Homologue from Bdellovibrio bacteriovorus: Insight into the Ligand Recognition Mechanism. Int. J. Mol. Sci. 2020, 21, 6785.

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