ArticleProceedings of the National Academy of Sciences of the United States of America2023
Disordered region encodes α-crystallin chaperone activity toward lens client γD-crystallin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Structural and functional characterization of sHsp from the marine cyanobacteriumBiochemistry and biophysics reports · 2026Article
- Heat shock proteins at the crossroads of endosomal trafficking pathways.Cell biology and toxicology · 2025Review
- Disorder with consequence: Phosphorylation sites in HSPB5 yield distinct structural outcomes.bioRxiv : the preprint server for biology · 2025Article
- Small heat shock protein HSPB5 uses disorder to bind zinc with high affinity.bioRxiv : the preprint server for biology · 2025Article
- Structural analyses define the molecular basis of clusterin chaperone function.Nature structural & molecular biology · 2025Article
- Mini-αA-crystallin protects a client lens protein from catastrophic aggregation due to heat stress.Protein science : a publication of the Protein Society · 2025Article
- Activation mechanism of small heat shock protein HSPB5 revealed by disease-associated mutants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanism of small heat shock protein client sequestration and induced polydispersity.Nature communications · 2025Article
- Dynamic fibrillar assembly of αB-crystallin induced by perturbation of the conserved NT-IXI motif resolved by cryo-EM.Nature communications · 2024Article
- Chaperone/Polymer Complexation of Protein-Based Fluorescent Nanoclusters against Silica Encapsulation-Induced Physicochemical Stresses.Biomacromolecules · 2024Article
- High-Performance Workflow for Identifying Site-Specific Crosslinks Originating from a Genetically Incorporated, Photoreactive Amino Acid.Journal of proteome research · 2024Article
- Aging of the eye: Lessons from cataracts and age-related macular degeneration.Ageing research reviews · 2024Review
- Roles of Nucleic Acids in Protein Folding, Aggregation, and Disease.ACS chemical biology · 2024Review
- The α-crystallin Chaperones Undergo a Quasi-ordered Co-aggregation Process in Response to Saturating Client Interaction.Journal of molecular biology · 2024Article
- Dynamic fibrillar assembly of αB-crystallin induced by perturbation of the conserved NT-IXI motif resolved by cryo-EM.bioRxiv : the preprint server for biology · 2024Article
- The major inducible small heat shock protein HSP20-3 in the tardigrade Ramazzottius varieornatus forms filament-like structures and is an active chaperone.Cell stress & chaperones · 2024Article
- HspB5 Chaperone Structure and Activity Are Modulated by Chemical-Scale Interactions in the ACD Dimer Interface.International journal of molecular sciences · 2023Article
- The beauty and complexity of the small heat shock proteins: a report on the proceedings of the fourth workshop on small heat shock proteins.Cell stress & chaperones · 2023Review
- Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Small heat-shock proteins (sHSPs) are a widely expressed family of ATP-independent molecular chaperones that are among the first responders to cellular stress. Mechanisms by which sHSPs delay aggregation of client proteins remain undefined. sHSPs have high intrinsic disorder content of up to ~60% and assemble into large, polydisperse homo- and hetero-oligomers, making them challenging structural and biochemical targets. Two sHSPs, HSPB4 and HSPB5, are present at millimolar concentrations in eye lens, where they are responsible for maintaining lens transparency over the lifetime of an organism. Together, HSPB4 and HSPB5 compose the hetero-oligomeric chaperone known as α-crystallin. To identify the determinants of sHSP function, we compared the effectiveness of HSPB4 and HSPB5 homo-oligomers and HSPB4/HSPB5 hetero-oligomers in delaying the aggregation of the lens protein γD-crystallin. In chimeric versions of HSPB4 and HSPB5, chaperone activity tracked with the identity of the 60-residue disordered N-terminal regions (NTR). A short 10-residue stretch in the middle of the NTR ("Critical sequence") contains three residues that are responsible for high HSPB5 chaperone activity toward γD-crystallin. These residues affect structure and dynamics throughout the NTR. Abundant interactions involving the NTR Critical sequence reveal it to be a hub for a network of interactions within oligomers. We propose a model whereby the NTR critical sequence influences local structure and NTR dynamics that modulate accessibility of the NTR, which in turn modulates chaperone activity.
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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 Socratic graph.