Evidence map›Paper›PMID 31004798›Full record

ArticleBiochimica et biophysica acta. Proteins and proteomics

Lipid-modulation of membrane insertion and refolding of the apoptotic inhibitor Bcl-xL.

Victor Vasquez-Montes, Mauricio Vargas-Uribe, Nitin K Pandey, Mykola V Rodnin, Ralf Langen, Alexey S Ladokhin

Abstract read
In one paragraph

Article in Biochimica et biophysica acta. Proteins and proteomics. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Lipids modulate the BH3-independent membrane targeting and activation of BAX and Bcl-xL.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  9. Article
  10. Article
  11. Article
  12. How bilayer properties influence membrane protein folding.Protein science : a publication of the Protein Society · 2020
    Review
  13. Article
  14. BCL-xL, a Mitochondrial Protein Involved in Successful Aging: FromInternational journal of molecular sciences · 2020
    Review
  15. Article
  16. 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

6 authors.

Victor Vasquez-MontesDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Mauricio Vargas-UribeDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Nitin K PandeyZilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA.
Mykola V RodninDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Ralf LangenZilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA.
Alexey S LadokhinDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: aladokhin@kumc.edu.

Funding

Membrane-Mediated Interactions of the Bcl-xL/Bid/Bax Triad of Apoptotic RegulatorsR01GM126778 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI LADOKHIN, ALEXEY, LANGEN, RALF · 2019 to 2022
$1.7M
NIGMS NIH HHS R01 GM126778
6 · The paper itself

Abstract

Bcl-xL is a member of the Bcl-2 family of apoptotic regulators, responsible for inhibiting the permeabilization of the mitochondrial outer membrane, and a promising anti-cancer target. Bcl-xL exists in the following conformations, each believed to play a role in the inhibition of apoptosis: (a) a soluble folded conformation, (b) a membrane-anchored (by its C-terminal α8 helix) form, which retains the same fold as in solution and (c) refolded membrane-inserted conformations, for which no structural data are available. Previous studies established that in the cell Bcl-xL exists in a dynamic equilibrium between soluble and membranous states, however, no direct evidence exists in support of either anchored or inserted conformation of the membranous state in vivo. In this in vitro study, we employed a combination of fluorescence and EPR spectroscopy to characterize structural features of the bilayer-inserted conformation of Bcl-xL and the lipid modulation of its membrane insertion transition. Our results indicate that the core hydrophobic helix α6 inserts into the bilayer without adopting a transmembrane orientation. This insertion disrupts the packing of Bcl-xL and releases the regulatory N-terminal BH4 domain (α1) from the rest of the protein structure. Our data demonstrate that both insertion and refolding of Bcl-xL are modulated by lipid composition, which brings the apparent pK

Indexed as

bcl-X ProteinElectron Spin Resonance SpectroscopyHumansLipid BilayersMembrane LipidsProtein DomainsBCL2L1 protein, humanbcl-X ProteinLipid BilayersMembrane Lipids

Identifiers

PMID31004798
PMCPMC6589348

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Registered trials

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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.