Evidence map›Paper›PMID 24652590›Full record

ArticleProtein science : a publication of the Protein Society2014

Membrane protein stability can be compromised by detergent interactions with the extramembranous soluble domains.

Zhengrong Yang, Chi Wang, Qingxian Zhou, Jianli An, Ellen Hildebrandt, Luba A Aleksandrov, John C Kappes, Lawrence J DeLucas, John R Riordan, Ina L Urbatsch and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

57 citing papers in PubMed, 108 citations in OpenAlex.

  1. Review
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  9. Review
  10. Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
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  15. High-Resolution Cryo-Electron Microscopy Structure Determination ofInternational journal of molecular sciences · 2024
    Article
  16. Article
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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

12 authors at 5 institutions in 1 country.

Zhengrong YangDepartment of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama; Center for Structural Biology, University of Alabama at Birmingham, Birmingham, Alabama.
Chi Wang
Qingxian Zhou
Jianli An
Ellen Hildebrandt
Luba A Aleksandrov
John C Kappes
Lawrence J DeLucas
John R Riordan
Ina L Urbatsch
John F Hunt
Christie G Brouillette
University of Alabama at Birmingham · USColumbia University · USTexas Tech University Health Sciences Center · USUniversity of North Carolina at Chapel Hill · USBirmingham VA Medical Center · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
University of Georgia ProjectU54GM094597 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI SZYPERSKI, THOMAS A. · 2010 to 2014
$36.9M
UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI David M. Bedwell · 2007 to 2026
$23.0M
Purinergic Control of CFTR-ENaC Interactions in Alveolar EpitheliaP01HL110873 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2012 to 2016
$10.7M
Restoration of mutant CFTR stability and functionR01DK051870 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BALCH, WILLIAM EDWARD · 1996 to 2020
$8.7M
MOLECULAR MECHANISMS OF CFTR FUNCTIONR01DK051619 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RIORDAN, JOHN R · 1997 to 2013
$3.0M
Understanding polyspecific drug binding in P-glycoproteinR15GM102928 · NIGMS · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI URBATSCH, INA L · 2012 to 2012
$347k
NCI NIH HHS P30 CA013148NHLBI NIH HHS P01 HL110873NIDDK NIH HHS P30 DK072482NIDDK NIH HHS R01 DK051619NIDDK NIH HHS R01 DK051870NIGMS NIH HHS R15 GM102928NIGMS NIH HHS U54 GM094597
6 · The paper itself

Abstract

Detergent interaction with extramembranous soluble domains (ESDs) is not commonly considered an important determinant of integral membrane protein (IMP) behavior during purification and crystallization, even though ESDs contribute to the stability of many IMPs. Here we demonstrate that some generally nondenaturing detergents critically destabilize a model ESD, the first nucleotide-binding domain (NBD1) from the human cystic fibrosis transmembrane conductance regulator (CFTR), a model IMP. Notably, the detergents show equivalent trends in their influence on the stability of isolated NBD1 and full-length CFTR. We used differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy to monitor changes in NBD1 stability and secondary structure, respectively, during titration with a series of detergents. Their effective harshness in these assays mirrors that widely accepted for their interaction with IMPs, i.e., anionic > zwitterionic > nonionic. It is noteworthy that including lipids or nonionic detergents is shown to mitigate detergent harshness, as will limiting contact time. We infer three thermodynamic mechanisms from the observed thermal destabilization by monomer or micelle: (i) binding to the unfolded state with no change in the native structure (all detergent classes); (ii) native state binding that alters thermodynamic properties and perhaps conformation (nonionic detergents); and (iii) detergent binding that directly leads to denaturation of the native state (anionic and zwitterionic). These results demonstrate that the accepted model for the harshness of detergents applies to their interaction with an ESD. It is concluded that destabilization of extramembranous soluble domains by specific detergents will influence the stability of some IMPs during purification.

Indexed as

Calorimetry, Differential ScanningCircular DichroismDetergentsMembrane ProteinsProtein DenaturationProtein FoldingProtein StabilityProtein Structure, SecondaryProtein Structure, TertiaryDetergentsMembrane ProteinsCDCFTRdetergent interactionDSCextramembrane domainmembrane proteinNBD1soluble domainthermal unfolding

Identifiers

PMID24652590
PMCPMC4093953
OpenAlexW1912840982

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.