Evidence map›Paper›PMID 37495662›Full record

ArticleCommunications biology2023

Rational engineering of an elevator-type metal transporter ZIP8 reveals a conditional selectivity filter critically involved in determining substrate specificity.

Yuhan Jiang, Zhen Li, Dexin Sui, Gaurav Sharma, Tianqi Wang, Keith MacRenaris, Hideki Takahashi, Kenneth Merz, Jian Hu

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Functional characterization of a novel ZIP8 variant causing impaired manganese homeostasis and congenital disorders of glycosylation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
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  10. Deorphanizing solute carriers inFrontiers in microbiology · 2024
    Article
  11. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Yuhan JiangDepartment of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
Zhen LiDepartment of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
Dexin SuiDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Gaurav SharmaDepartment of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
Tianqi WangDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Keith MacRenarisDepartment of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA.
Hideki TakahashiDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.ORCID http://orcid.org/0000-0001-8439-0533
Kenneth MerzDepartment of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.
Jian HuDepartment of Chemistry, Michigan State University, East Lansing, MI, 48824, USA. hujian1@msu.edu.ORCID http://orcid.org/0000-0001-6657-9826
Michigan State University · US

Funding

TR&D Project 3: Photoacoustic Detection of Metal Fluxes at the Tissue LevelP41GM135018 · NIGMS · NORTHWESTERN UNIVERSITY · PI MACRENARIS, KEITH W · 2020 to 2024
$5.8M
METALLOREGULATION BY MERR AND FUR PROTEIN FAMILIESR37GM038784 · NIGMS · NORTHWESTERN UNIVERSITY · PI O'HALLORAN, THOMAS V · 2001 to 2010
$3.6M
Metalloregulation by MerR and Fur Protein FamiliesR01GM038784 · NIGMS · NORTHWESTERN UNIVERSITY · PI O'HALLORAN, THOMAS V · 1992 to 2025
$3.5M
Regulatory Roles of Zinc Fluxes in Metalloprotein Occupancy and Cell Cycle ProgressionR01GM115848 · NIGMS · NORTHWESTERN UNIVERSITY · PI O'HALLORAN, THOMAS V · 2015 to 2025
$2.8M
Modeling Transition Metal Ion Binding to ProteinsR01GM130641 · NIGMS · MICHIGAN STATE UNIVERSITY · PI KENNETH M. MERZ · 2019 to 2026
$2.5M
Transport, substrate specificity and regulation mechanisms of the ZIP transition metal transportersR35GM140931 · NIGMS · MICHIGAN STATE UNIVERSITY · PI HU, JIAN · 2021 to 2025
$1.7M
Structural and Mechanistic Characterization of the ZIP Metal TransportersR01GM129004 · NIGMS · MICHIGAN STATE UNIVERSITY · PI HU, JIAN · 2018 to 2020
$593k
NIGMS NIH HHS P41 GM135018NIGMS NIH HHS R01 GM038784NIGMS NIH HHS R01 GM115848NIGMS NIH HHS R01 GM129004NIGMS NIH HHS R01 GM130641NIGMS NIH HHS R35 GM140931NIGMS NIH HHS R37 GM038784
6 · The paper itself

Abstract

Engineering of transporters to alter substrate specificity as desired holds great potential for applications, including metabolic engineering. However, the lack of knowledge on molecular mechanisms of substrate specificity hinders designing effective strategies for transporter engineering. Here, we applied an integrated approach to rationally alter the substrate preference of ZIP8, a Zrt-/Irt-like protein (ZIP) metal transporter with multiple natural substrates, and uncovered the determinants of substrate specificity. By systematically replacing the differentially conserved residues with the counterparts in the zinc transporter ZIP4, we created a zinc-preferring quadruple variant (Q180H/E343H/C310A/N357H), which exhibited largely reduced transport activities towards Cd

Indexed as

MetalsZincMembrane Transport ProteinsMolecular ConformationSubstrate SpecificityMembrane Transport ProteinsMetalsZinc

Identifiers

PMID37495662
PMCPMC10372143
OpenAlexW4385278527

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.