Evidence map›Paper›PMID 34138981›Full record

ArticlePLoS pathogens2021

Structurally distinct external solvent-exposed domains drive replication of major human prions.

Mohammad Khursheed Siddiqi, Chae Kim, Tracy Haldiman, Miroslava Kacirova, Benlian Wang, Jen Bohon, Mark R Chance, Janna Kiselar, Jiri G Safar

Abstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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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

9 authors.

Mohammad Khursheed SiddiqiDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0002-6522-1643
Chae KimDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Tracy HaldimanDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Miroslava KacirovaDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0002-1478-1712
Benlian WangDepartment of Nutrition, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0002-6108-0417
Jen BohonDepartment of Nutrition, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0002-7664-9899
Mark R ChanceDepartment of Nutrition, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0002-2991-6405
Janna KiselarDepartment of Nutrition, Case Western Reserve University, Cleveland, Ohio, United States of America.
Jiri G SafarDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0003-2209-0070

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Amar Desai · 1987 to 2026
$142.3M
Replication mechanism of human prionsR01NS103848 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI SAFAR, JIRI G., SUREWICZ, WITOLD K · 2018 to 2022
$2.6M
Orbitrap Fusion Lumos Tribrid Mass SpectrometerS10OD026882 · OD · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2019 to 2019
$1.0M
CDC HHS NU38 CK000480NCI NIH HHS P30 CA043703NIH HHS S10 OD026882NINDS NIH HHS R01 NS103848
6 · The paper itself

Abstract

There is a limited understanding of structural attributes that encode the iatrogenic transmissibility and various phenotypes of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD). Here we report the detailed structural differences between major sCJD MM1, MM2, and VV2 prions determined with two complementary synchrotron hydroxyl radical footprinting techniques-mass spectrometry (MS) and conformation dependent immunoassay (CDI) with a panel of Europium-labeled antibodies. Both approaches clearly demonstrate that the phenotypically distant prions differ in a major way with regard to their structural organization, and synchrotron-generated hydroxyl radicals progressively inhibit their seeding potency in a strain and structure-specific manner. Moreover, the seeding rate of sCJD prions is primarily determined by strain-specific structural organization of solvent-exposed external domains of human prion particles that control the seeding activity. Structural characteristics of human prion strains suggest that subtle changes in the organization of surface domains play a critical role as a determinant of human prion infectivity, propagation rate, and targeting of specific brain structures.

Indexed as

Creutzfeldt-Jakob SyndromeHumansProtein ConformationProtein DomainsProtein IsoformsPrPSc ProteinsProtein IsoformsPrPSc Proteins

Identifiers

PMID34138981
PMCPMC8211289

What OpenQuestion holds

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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.