Falcon supports HSP26 as an ATP-independent small heat-shock holdase chaperone that suppresses aggregation of nonnative proteins.

Machine-learning-based association rule mining methodology that propagates GO terms from UniProtKB feature evidence. Used here as the source of the IEA "protein folding" annotation for HSP26; the rule is broader than the experimentally supported holdase activity and is over-annotated in this case.

HSP26 is a temperature-regulated molecular chaperone. The 24-mer storage complex dissociates at heat shock temperatures, and this dissociation is a prerequisite for efficient chaperone activity. Binding of non-native proteins to dissociated Hsp26 produces large globular assemblies with 1:2 substrate:Hsp26 stoichiometry.

Large-scale immunolocalization study of 2744 yeast proteins. HSP26 detected in cytoplasm.

Genome-wide TAP-tag affinity purification/MS screen for yeast protein complexes. HSP26 detected as co-purifying with SSA2 and VMA2.

Large-scale TAP-tag study of yeast protein complexes. Multiple HSP26 interaction partners detected including ADH3, EMW1, FUS3, NEW1, POL32, RNR1, RTT101, SGV1, SME1, TFB4, UPC2, VMA2.

Cryo-EM structure of Hsp26 reveals two distinct 24-subunit forms with tetrahedral symmetry. Subunits form asymmetric dimers that assemble via trimeric contacts. C-terminal tails form 3-fold contacts. Hinge points between domains provide flexibility for supercomplex formation with non-native proteins.

High-quality binary yeast interactome. HSP26-HSP26 self-interaction confirmed.

Comprehensive TAP-tag analysis of all 63 yeast chaperones. HSP26 classified as a "specific" chaperone with fewer than 200 non-chaperone interactors, consistent with selective holdase function rather than promiscuous chaperoning.

HSP26 identified as novel RNA-binding protein by protein microarray screen and validated by IP-microarray. Co-purified with 279 specific mRNAs. Lacks known RNA-binding domain. Described among "unexpected" RBPs with "day jobs" as enzymes or chaperones.

Yeast heat stress granules contain mRNA, translation machinery, and molecular chaperones. Heat-SGs coassemble with aggregates of misfolded proteins. Disassembly requires Hsp104 and Hsp70 activity.

Quantitative mitochondrial proteomics detected HSP26 in isolated mitochondrial fractions.

HSP26 found in complexes >500 kD. Intracellular localization depends on metabolic state: in glucose-grown log-phase cells after heat shock, concentrates in nuclei; in stationary-phase cells or cells grown in galactose/acetate, distributed throughout cytoplasm.

Proteomic analysis of stress granule cores reveals molecular chaperones as conserved components. ATP is required for stress granule assembly and dynamics.