Evidence map›Paper›PMID 27573840›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Conserved methionine dictates substrate preference in Nramp-family divalent metal transporters.

Aaron T Bozzi, Lukas B Bane, Wilhelm A Weihofen, Anne L McCabe, Abhishek Singharoy, Christophe J Chipot, Klaus Schulten, Rachelle Gaudet

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 98 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Determinants of metal import and specificity in a bacterial transporter.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Iron from the gut: the role of divalent metal transporter 1.Journal of clinical biochemistry and nutrition · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. A weak allele of OsNRAMP5 for safer rice.Journal of experimental botany · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Aaron T BozziDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;
Lukas B BaneDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;
Wilhelm A WeihofenDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;
Anne L McCabeDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;
Abhishek SingharoyBeckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
Christophe J ChipotLaboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche CNRS n°7565, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy cedex, France; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Klaus SchultenBeckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Rachelle GaudetDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; gaudet@mcb.harvard.edu.ORCID 0000-0002-9177-054X
Harvard University · USUniversity of Illinois Urbana-Champaign · USCentre National de la Recherche Scientifique · FR

Funding

WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI TAJKHORSHID, EMAD · 2012 to 2021
$19.0M
Training in Molecular, Cellular, and Chemical BiologyT32GM007598 · NIGMS · HARVARD UNIVERSITY · PI DULAC, CATHERINE · 1985 to 2019
$16.2M
NIGMS NIH HHS P41 GM104601NIGMS NIH HHS T32 GM007598
6 · The paper itself

Abstract

Natural resistance-associated macrophage protein (Nramp) family transporters catalyze uptake of essential divalent transition metals like iron and manganese. To discriminate against abundant competitors, the Nramp metal-binding site should favor softer transition metals, which interact either covalently or ionically with coordinating molecules, over hard calcium and magnesium, which interact mainly ionically. The metal-binding site contains an unusual, but conserved, methionine, and its sulfur coordinates transition metal substrates, suggesting a vital role in their transport. Using a bacterial Nramp model system, we show that, surprisingly, this conserved methionine is dispensable for transport of the physiological manganese substrate and similar divalents iron and cobalt, with several small amino acid replacements still enabling robust uptake. Moreover, the methionine sulfur's presence makes the toxic metal cadmium a preferred substrate. However, a methionine-to-alanine substitution enables transport of calcium and magnesium. Thus, the putative evolutionary pressure to maintain the Nramp metal-binding methionine likely exists because it-more effectively than any other amino acid-increases selectivity for low-abundance transition metal transport in the presence of high-abundance divalents like calcium and magnesium.

Indexed as

Amino Acid SequenceBiological TransportCalciumCations, DivalentCation Transport ProteinsCobaltDeinococcusIon TransportIronManganeseMethionineNatural Resistance-associated Macrophage Protein 1Substrate SpecificityCalciumCations, DivalentCation Transport ProteinsCobaltIronManganeseMethionineNatural Resistance-associated Macrophage Protein 1divalent metal transporter DMT1hard-soft acid-base theoryion selectivity filtersMntHtransition metals

Identifiers

PMID27573840
PMCPMC5027461
OpenAlexW2513826178

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.