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Nutritional immunity: homology modeling of Nramp metal import

Cellier, Mathieu ORCID logoORCID: https://orcid.org/0000-0002-6084-434X (2012). Nutritional immunity: homology modeling of Nramp metal import Advances in Experimental Medicine and Biology , vol. 946 . pp. 335-51. DOI: 10.1007/978-1-4614-0106-3_19.

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Résumé


The Natural resistance-associated macrophage proteins (Nramp1 and 2) are proton-dependent solute carriers of divalent metals such as Fe(2+) and Mn(2+) (Slc11a1 and 2). Their expression in both resting and microbicidal macrophages which metabolize iron differently, raises questions about Nramp mechanism of Me(2+) transport and its impact in distinct phenotypic contexts. We developed a low resolution 3D model for Slc11 based on detailed phylogeny and remote homology threading using Escherichia coli Nramp homolog (proton-dependent Mn(2+) transporter, MntH) as experimental system. The predicted fold is consistent with determinations of transmembrane topology and activity; it indicates Slc11 carriers are part of the LeuT superfamily. Homology implies that inverted structural symmetry facilitates Slc11 H(+)-driven Me(2+) import and provides a 3D framework to test structure-activity relationships in macrophages and study functional evolution of MntH/Nramp (Slc11) carriers.

Type de document: Article
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 06 mars 2024 15:26
Dernière modification: 06 mars 2024 15:26
URI: https://espace.inrs.ca/id/eprint/13996

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