Evidence map›Paper›PMID 34876699›Full record

ArticleCommunications biology2021

Conformational dynamics of free and membrane-bound human Hsp70 in model cytosolic and endo-lysosomal environments.

Valeria Calvaresi, Line T Truelsen, Sidsel B Larsen, Nikolaj H T Petersen, Thomas Kirkegaard, Kasper D Rand

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Lysosomal Repair in Health and Disease.Journal of cellular physiology · 2025
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Probing Antibody Structures by Hydrogen/Deuterium Exchange Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
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.

Valeria CalvaresiProtein Analysis Group, Department of Pharmacy, University of Copenhagen, 2100, Copenhagen O, Denmark.
Line T TruelsenProtein Analysis Group, Department of Pharmacy, University of Copenhagen, 2100, Copenhagen O, Denmark.
Sidsel B LarsenProtein Analysis Group, Department of Pharmacy, University of Copenhagen, 2100, Copenhagen O, Denmark.
Nikolaj H T PetersenOrphazyme A/S, Copenhagen, Denmark.
Thomas KirkegaardOrphazyme A/S, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5931-263X
Kasper D RandProtein Analysis Group, Department of Pharmacy, University of Copenhagen, 2100, Copenhagen O, Denmark. kasper.rand@sund.ku.dk.ORCID http://orcid.org/0000-0002-6337-5489
University of Copenhagen · DKOrphazyme (Denmark) · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The binding of the major stress-inducible human 70-kDa heat shock protein (Hsp70) to the anionic phospholipid bis-(monoacylglycero)-phosphate (BMP) in the lysosomal membrane is crucial for its impact on cellular pathology in lysosomal storage disorders. However, the conformational features of this protein-lipid complex remain unclear. Here, we apply hydrogen-deuterium exchange mass spectrometry (HDX-MS) to describe the dynamics of the full-length Hsp70 in the cytosol and its conformational changes upon translocation into lysosomes. Using wild-type and W90F mutant proteins, we also map and discriminate the interaction of Hsp70 with BMP and other lipid components of the lysosomal membrane. We identify the N-terminal of the nucleotide binding domain (residues 87-118) as the primary orchestrator of BMP interaction. We show that the conformation of this domain is significantly reorganized in the W90F mutant, explaining its inability to stabilize lysosomal membranes. Overall, our results reveal important new molecular details of the protective effect of Hsp70 in lysosomal storage diseases, which, in turn, could guide future drug development.

Indexed as

CytosolHSP70 Heat-Shock ProteinsHumansLysophospholipidsLysosomesMolecular ConformationMonoglyceridesbis(monoacylglyceryl)phosphateHSP70 Heat-Shock ProteinsLysophospholipidsMonoglycerides

Identifiers

PMID34876699
PMCPMC8651726
OpenAlexW4200095380

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.