Evidence map›Paper›PMID 30608666›Full record

ArticleChemical reviews2019

Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.

Justin T Marinko, Hui Huang, Wesley D Penn, John A Capra, Jonathan P Schlebach, Charles R Sanders

Open access · greenAbstract read
In one paragraph

Article in Chemical reviews, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed
11.9field-weighted citation impact, top 1% 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

153 citing papers in PubMed, 258 citations in OpenAlex.

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  8. bioRxiv : the preprint server for biology · 2026
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  14. Bridging Scales: Coarse-Grained Protein Models in Computational Biology.Advances in experimental medicine and biology · 2026
    Review
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93 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

Justin T MarinkoDepartment of Biochemistry , Vanderbilt University , Nashville , Tennessee 37240 , United States.
Hui HuangDepartment of Biochemistry , Vanderbilt University , Nashville , Tennessee 37240 , United States.
Wesley D PennDepartment of Chemistry , Indiana University , Bloomington , Indiana 47405 , United States.
John A CapraCenter for Structural Biology , Vanderbilt University , Nashville , Tennessee 37240 , United States.
Jonathan P SchlebachDepartment of Chemistry , Indiana University , Bloomington , Indiana 47405 , United States.ORCID 0000-0003-0955-7633
Charles R SandersDepartment of Biochemistry , Vanderbilt University , Nashville , Tennessee 37240 , United States.ORCID 0000-0003-2046-2862
Vanderbilt University · USIndiana University Bloomington · 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
MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Folding, Misfolding, and Function of PMP22R01NS095989 · NINDS · VANDERBILT UNIVERSITY · PI Bruce D Carter, CHARLES R SANDERS · 2016 to 2026
$4.6M
Roles of Cholesterol and Membrane Nanodomains in the Amyloidogenic PathwayRF1AG056147 · NIA · VANDERBILT UNIVERSITY · PI KENWORTHY, ANNE K, SANDERS, CHARLES R · 2017 to 2017
$3.6M
The Evolution of Gene Regulation and Human DiseaseR35GM127087 · NIGMS · VANDERBILT UNIVERSITY · PI John Anthony Capra · 2018 to 2026
$3.2M
Topological Energetics and the Cellular Quality Control of Integral Membrane ProteinsR01GM129261 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI SCHLEBACH, JONATHAN PATRICK · 2018 to 2022
$1.5M
NHLBI NIH HHS R01 HL122010NIA NIH HHS RF1 AG056147NIGMS NIH HHS R01 GM129261NIGMS NIH HHS R35 GM127087NIGMS NIH HHS T32 GM008320NINDS NIH HHS R01 NS095989
6 · The paper itself

Abstract

Advances over the past 25 years have revealed much about how the structural properties of membranes and associated proteins are linked to the thermodynamics and kinetics of membrane protein (MP) folding. At the same time biochemical progress has outlined how cellular proteostasis networks mediate MP folding and manage misfolding in the cell. When combined with results from genomic sequencing, these studies have established paradigms for how MP folding and misfolding are linked to the molecular etiologies of a variety of diseases. This emerging framework has paved the way for the development of a new class of small molecule "pharmacological chaperones" that bind to and stabilize misfolded MP variants, some of which are now in clinical use. In this review, we comprehensively outline current perspectives on the folding and misfolding of integral MPs as well as the mechanisms of cellular MP quality control. Based on these perspectives, we highlight new opportunities for innovations that bridge our molecular understanding of the energetics of MP folding with the nuanced complexity of biological systems. Given the many linkages between MP misfolding and human disease, we also examine some of the exciting opportunities to leverage these advances to address emerging challenges in the development of therapeutics and precision medicine.

Indexed as

HumansKineticsMembrane ProteinsModels, MolecularProtein ConformationProtein FoldingProtein StabilityProteostasisProteostasis DeficienciesThermodynamicsMembrane Proteins

Identifiers

PMID30608666
PMCPMC6506414
OpenAlexW2907116351

What Socratic 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 Socratic graph.