Evidence map›Paper›PMID 40168989›Full record

ReviewCell chemical biology2025

Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens.

Silas T Miller, Christian B Macdonald, Srivatsan Raman

Abstract readReview
In one paragraph

Review in Cell chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Article
  3. Advanced optical microscopy methods forBiophysical reviews · 2025
    Review
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

3 authors.

Silas T MillerCellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53706, USA.
Christian B MacdonaldDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Srivatsan RamanDOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: sraman4@wisc.edu.

Funding

Understanding molecular rules governing protein allostery by deep mutational scanningDP2GM132682 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI RAMAN, SRIVATSAN · 2018 to 2018
$2.1M
Connecting structure and fitness landscapes to overcome antibiotic resistanceF32GM152977 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MACDONALD, CHRISTIAN BERNARD · 2023 to 2024
$146k
NIGMS NIH HHS DP2 GM132682NIGMS NIH HHS F32 GM152977
6 · The paper itself

Abstract

Promiscuous membrane transporters play vital roles across domains of life, mediating the uptake and efflux of structurally and chemically diverse substrates. Although many transporter structures have been solved, the fundamental rules of polyspecific transport remain inscrutable. In recent years, high-throughput genetic screens have solidified as powerful tools for comprehensive, unbiased measurements of variant function and hypothesis generation, but have had infrequent application and limited impact in the transporter field. In this primer, we describe the principles of high-throughput screening methods available for studying polyspecific transporters and comment on the necessity and potential of high-throughput methods for deciphering these transporters in particular. We present several screening approaches which could provide a fundamental understanding of the molecular basis of function and promiscuity in transporters. We further posit how this knowledge can be leveraged to design inhibitors that combat multidrug resistance and engineer transporters as needed tools for synthetic biology and biotechnology applications.

Indexed as

High-Throughput Screening AssaysMembrane Transport ProteinsProtein EngineeringHumansMutationMembrane Transport Proteinsefflux pump inhibitorsEPIsfunctional promiscuityhigh-throughput screeningmembrane transporterspolyspecificitytransporter engineering

Identifiers

PMID40168989
PMCPMC13040374

What OpenQuestion holds

Textmetadata
LicenceTDM
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.