Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane import
Determination of the crystal structure of ScaDMT, a member of the Slc11 family, provided opportunity to advance understanding of proton-dependent metal-ion uptake by interfacing Slc11 molecular evolution and structural biology. Slc11 carriers belong to the ancient and broadly distributed APC superfa...
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doaj-c84c7fad609f4707b14c22e617ea799c2020-11-24T21:29:07ZengAIMS PressAIMS Biophysics2377-90982016-06-013228631810.3934/biophy.2016.2.286biophys-03-00286Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane importMathieu F. M. Cellier0Inrs-Institut Armand-Frappier, 531, Bd des prairies, Laval, QC H7V 1B7, CanadaDetermination of the crystal structure of ScaDMT, a member of the Slc11 family, provided opportunity to advance understanding of proton-dependent metal-ion uptake by interfacing Slc11 molecular evolution and structural biology. Slc11 carriers belong to the ancient and broadly distributed APC superfamily characterized by the pseudo-symmetric LeuT-fold. This fold comprises two topologically inverted repeats (protomers) that exchange alternate configurations during carrier cycling. Examining ScaDMT molecule inserted within a model membrane allowed to pinpoint residues that may interact with surrounding lipid solvent molecules. Three-dimensional mapping of Slc11-specific sites demonstrated they distribute at the protomer interface, along the transmembrane ion-conduction pathway. Functional sites were predicted by modeling hypothetical ScaDMT alternate conformers based on APC templates; these candidate homologous sites were found to co-localize with Slc11-specific sites, a distribution pattern that fits the functional diversity in the APC superfamily. Sites that diverged among eukaryotic Slc11 (Nramp) types were located in transmembrane helices that may participate in discrete steps during co-substrate translocation, suggesting these sites influence transport activity. Adding some functional dimension to Slc11 carrier evolution will inform molecular understanding of metal-ion transport selectivity and regulation, Slc11 physiological roles and contribution to host resistance to microbial infection.http://www.aimspress.com/biophysics/article/810/fulltext.htmlmetal-ionmembrane transportproton-couplingsolute carrier family 11proton-dependent Mn transporternatural resistance-associated macrophage proteindivalent metal transporterLeuT foldamino acid-polyamine-organo-cation superfamily. |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mathieu F. M. Cellier |
spellingShingle |
Mathieu F. M. Cellier Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane import AIMS Biophysics metal-ion membrane transport proton-coupling solute carrier family 11 proton-dependent Mn transporter natural resistance-associated macrophage protein divalent metal transporter LeuT fold amino acid-polyamine-organo-cation superfamily. |
author_facet |
Mathieu F. M. Cellier |
author_sort |
Mathieu F. M. Cellier |
title |
Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane import |
title_short |
Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane import |
title_full |
Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane import |
title_fullStr |
Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane import |
title_full_unstemmed |
Evolutionary analysis of Slc11 mechanism of proton-coupled metal-ion transmembrane import |
title_sort |
evolutionary analysis of slc11 mechanism of proton-coupled metal-ion transmembrane import |
publisher |
AIMS Press |
series |
AIMS Biophysics |
issn |
2377-9098 |
publishDate |
2016-06-01 |
description |
Determination of the crystal structure of ScaDMT, a member of the Slc11 family, provided opportunity to advance understanding of proton-dependent metal-ion uptake by interfacing Slc11 molecular evolution and structural biology. Slc11 carriers belong to the ancient and broadly distributed APC superfamily characterized by the pseudo-symmetric LeuT-fold. This fold comprises two topologically inverted repeats (protomers) that exchange alternate configurations during carrier cycling. Examining ScaDMT molecule inserted within a model membrane allowed to pinpoint residues that may interact with surrounding lipid solvent molecules. Three-dimensional mapping of Slc11-specific sites demonstrated they distribute at the protomer interface, along the transmembrane ion-conduction pathway. Functional sites were predicted by modeling hypothetical ScaDMT alternate conformers based on APC templates; these candidate homologous sites were found to co-localize with Slc11-specific sites, a distribution pattern that fits the functional diversity in the APC superfamily. Sites that diverged among eukaryotic Slc11 (Nramp) types were located in transmembrane helices that may participate in discrete steps during co-substrate translocation, suggesting these sites influence transport activity. Adding some functional dimension to Slc11 carrier evolution will inform molecular understanding of metal-ion transport selectivity and regulation, Slc11 physiological roles and contribution to host resistance to microbial infection. |
topic |
metal-ion membrane transport proton-coupling solute carrier family 11 proton-dependent Mn transporter natural resistance-associated macrophage protein divalent metal transporter LeuT fold amino acid-polyamine-organo-cation superfamily. |
url |
http://www.aimspress.com/biophysics/article/810/fulltext.html |
work_keys_str_mv |
AT mathieufmcellier evolutionaryanalysisofslc11mechanismofprotoncoupledmetaliontransmembraneimport |
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1725967248614490112 |