ArticleThe Journal of biological chemistry2019
The endoplasmic reticulum (ER) chaperones BiP and Grp94 selectively associate when BiP is in the ADP conformation.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
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.
Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Immunoglobulin binding protein (BiP) forms two types of dimers.Protein science : a publication of the Protein Society · 2026Article
- Multi-omics network reconstruction with collaborative graphical lasso.Bioinformatics (Oxford, England) · 2026Article
- Heat shock protein Gp96 (Grp94) in malaria: functional insights at the host-parasite interface and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- Conformational plasticity of a BiP-GRP94 chaperone complex.Nature structural & molecular biology · 2025Article
- The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery.Trends in pharmacological sciences · 2025Review
- Mechanism of client loading from BiP to Grp94 and its disruption by select inhibitors.Nature communications · 2025Article
- Hsp90, a team player in protein quality control and the stress response in bacteria.Microbiology and molecular biology reviews : MMBR · 2024Review
- Structural transitions modulate the chaperone activities of Grp94.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- J-domain Proteins form Binary Complexes with Hsp90 and Ternary Complexes with Hsp90 and Hsp70.Journal of molecular biology · 2023Article
- Insight into the Nucleotide Based Modulation of the Grp94 Molecular Chaperone Using Multiscale Dynamics.The journal of physical chemistry. B · 2023Article
- Insulin secretion deficits in a Prader-Willi syndrome β-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones.PLoS genetics · 2023Article
- A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.Development (Cambridge, England) · 2023Article
- Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation.The Journal of biological chemistry · 2022Article
- Uncoupling the Hsp90 and DnaK chaperone activities revealed the in vivo relevance of their collaboration in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- [Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19].Revista medica del Instituto Mexicano del Seguro Social · 2022Review
- The endoplasmic reticulum chaperone BiP is a closure-accelerating cochaperone of Grp94.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- The Hsp70-Hsp90 go-between Hop/Stip1/Sti1 is a proteostatic switch and may be a drug target in cancer and neurodegeneration.Cellular and molecular life sciences : CMLS · 2021Review
- The ER Chaperones BiP and Grp94 Regulate the Formation of Insulin-Like Growth Factor 2 (IGF2) Oligomers.Journal of molecular biology · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hsp70 and Hsp90 chaperones are critical for protein quality control in the cytosol, whereas organelle-specific Hsp70/Hsp90 paralogs provide similar protection for mitochondria and the endoplasmic reticulum (ER). Cytosolic Hsp70/Hsp90 can operate sequentially with Hsp90 selectively associating with Hsp70 after Hsp70 is bound to a client protein. This observation has long suggested that Hsp90 could have a preference for interacting with clients at their later stages of folding. However, recent work has shown that cytosolic Hsp70/Hsp90 can directly interact even in the absence of a client, which opens up an alternative possibility that the ordered interactions of Hsp70/Hsp90 with clients could be a consequence of regulated changes in the direct interactions between Hsp70 and Hsp90. However, it is unknown how such regulation could occur mechanistically. Here, we find that the ER Hsp70/Hsp90 (BiP/Grp94) can form a direct complex in the absence of a client. Importantly, the direct interaction between BiP and Grp94 is nucleotide-specific, with BiP and Grp94 having higher affinity under ADP conditions and lower affinity under ATP conditions. We show that this nucleotide-specific association between BiP and Grp94 is largely due to the conformation of BiP. When BiP is in the ATP conformation its substrate-binding domain blocks Grp94; in contrast, Grp94 can readily associate with the ADP conformation of BiP, which represents the client-bound state of BiP. Our observations provide a mechanism for the sequential involvement of BiP and Grp94 in client folding where the conformation of BiP provides the signal for the subsequent recruitment of Grp94.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.