Evidence map›Paper›PMID 33640379›Full record

ArticleBiophysical journal2021

Structural determinants of cholesterol recognition in helical integral membrane proteins.

Brennica Marlow, Georg Kuenze, Bian Li, Charles R Sanders, Jens Meiler

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

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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

5 authors at 1 institution in 2 countries.

Brennica MarlowCenter for Structural Biology, Vanderbilt University, Nashville, Tennessee; Chemical and Physical Biology Program, Vanderbilt University, Nashville, Tennessee.
Georg KuenzeCenter for Structural Biology, Vanderbilt University, Nashville, Tennessee; Department of Chemistry, Vanderbilt University, Nashville, Tennessee; Institute for Drug Discovery, Leipzig University Medical School, Leipzig, Germany.
Bian LiCenter for Structural Biology, Vanderbilt University, Nashville, Tennessee; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee.
Charles R SandersCenter for Structural Biology, Vanderbilt University, Nashville, Tennessee; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee.
Jens MeilerCenter for Structural Biology, Vanderbilt University, Nashville, Tennessee; Chemical and Physical Biology Program, Vanderbilt University, Nashville, Tennessee; Department of Chemistry, Vanderbilt University, Nashville, Tennessee; Institute for Drug Discovery, Leipzig University Medical School, Leipzig, Germany. Electronic address: jens@meilerlab.org.
Vanderbilt University · US

Funding

Decrypting Variants of Uncertain Significance in Long-QT SyndromeR01HL122010 · NHLBI · VANDERBILT UNIVERSITY · PI GEORGE, ALFRED L., SANDERS, CHARLES R · 2014 to 2025
$15.5M
Membrane Protein Structure Elucidation from sparse NMR data (KAMP)R01GM080403 · NIGMS · VANDERBILT UNIVERSITY · PI MEILER, JENS · 2007 to 2019
$3.0M
NHLBI NIH HHS R01 HL122010NIGMS NIH HHS R01 GM080403
6 · The paper itself

Abstract

Cholesterol is an integral component of mammalian membranes. It has been shown to modulate membrane fluidity and dynamics and alter integral membrane protein function. However, understanding the molecular mechanisms of how cholesterol impacts protein function is complicated by limited and conflicting structural data. Because of the nature of the crystallization and cryo-EM structure determination, it is difficult to distinguish between specific and biologically relevant interactions and a nonspecific association. The only widely recognized search algorithm for cholesterol-integral-membrane-protein interaction sites is sequence based, i.e., searching for the so-called "Cholesterol Recognition/interaction Amino acid Consensus" motif. Although these motifs are present in numerous integral membrane proteins, there is inconclusive evidence to support their necessity or sufficiency for cholesterol binding. Here, we leverage the increasing number of experimental cholesterol-integral-membrane-protein structures to systematically analyze putative interaction sites based on their spatial arrangement and evolutionary conservation. This analysis creates three-dimensional representations of general cholesterol interaction sites that form clusters across multiple integral membrane protein classes. We also classify cholesterol-integral-membrane-protein interaction sites as either likely-specific or nonspecific. Information gleaned from our characterization will eventually enable a structure-based approach to predict and design cholesterol-integral-membrane-protein interaction sites.

Indexed as

CholesterolMembrane ProteinsAmino Acid MotifsAnimalsMembrane FluidityProtein BindingCholesterolMembrane Proteins

Identifiers

PMID33640379
PMCPMC8204209
OpenAlexW3130734118

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.