Evidence map›Paper›PMID 33046906›Full record

ArticleNature structural & molecular biology2020

The structure of a calsequestrin filament reveals mechanisms of familial arrhythmia.

Erron W Titus, Frederick H Deiter, Chenxu Shi, Julianne Wojciak, Melvin Scheinman, Natalia Jura, Rahul C Deo

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 21 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

7 authors at 2 institutions in 1 country.

Erron W TitusCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. erron.titus@ucsf.edu.ORCID http://orcid.org/0000-0001-6868-9121
Frederick H DeiterCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4454-6489
Chenxu ShiCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Julianne WojciakDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Melvin ScheinmanDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Natalia JuraCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5129-641X
Rahul C DeoCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. rdeo@bwh.harvard.edu.ORCID http://orcid.org/0000-0002-2791-9434
University of California, San Francisco · USBrigham and Women's Hospital · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI MARC ALLAIRE · 2017 to 2026
$28.6M
Eliminating Critical Systematic Errors In Structural Biology With Next-Generation SimulationR01GM124149 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HOLTON, JAMES M · 2017 to 2024
$2.5M
Resolving Incomplete Penetrance in the Cardiomyopathies and ChannelopathiesDP2HL123228 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEO, RAHUL CHANDRAKANT · 2013 to 2013
$2.4M
Cardiac Calsequestrin Filament Dynamics in Catecholaminergic Polymorphic Ventricular TachycardiaF30HL137329 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TITUS, ERRON WILCOX · 2017 to 2020
$112k
NHLBI NIH HHS DP2 HL123228NHLBI NIH HHS F30 HL137329NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R01 GM124149NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

Mutations in the calcium-binding protein calsequestrin cause the highly lethal familial arrhythmia catecholaminergic polymorphic ventricular tachycardia (CPVT). In vivo, calsequestrin multimerizes into filaments, but there is not yet an atomic-resolution structure of a calsequestrin filament. We report a crystal structure of a human cardiac calsequestrin filament with supporting mutational analysis and in vitro filamentation assays. We identify and characterize a new disease-associated calsequestrin mutation, S173I, that is located at the filament-forming interface, and further show that a previously reported dominant disease mutation, K180R, maps to the same surface. Both mutations disrupt filamentation, suggesting that disease pathology is due to defects in multimer formation. An ytterbium-derivatized structure pinpoints multiple credible calcium sites at filament-forming interfaces, explaining the atomic basis of calsequestrin filamentation in the presence of calcium. Our study thus provides a unifying molecular mechanism through which dominant-acting calsequestrin mutations provoke lethal arrhythmias.

Indexed as

AdultBinding SitesCalciumCalcium-Binding ProteinsCalsequestrinCloning, MolecularCrystallography, X-RayEscherichia coliFemaleGene ExpressionGenes, DominantGenetic VectorsHumansKineticsMaleMiddle AgedCalciumCalcium-Binding ProteinsCalsequestrinCASQ1 protein, humanCASQ2 protein, humanMitochondrial ProteinsRecombinant Proteins

Identifiers

PMID33046906
PMCPMC7718342
OpenAlexW3092103467

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.