sHSP

Small heat shock proteins, abbreviated sHSPs, are a diverse family of molecular chaperones found in nearly all organisms. They function as ATP-independent holdases that prevent aggregation of denatured proteins during cellular stress, such as heat, oxidative stress, or desiccation. By binding exposed hydrophobic regions on unfolded polypeptides, sHSPs keep clients in a refolding-competent state and cooperate with ATP-dependent chaperones like Hsp70 to restore proteostasis.

Most sHSPs share a conserved central alpha-crystallin domain flanked by flexible N- and C-terminal extensions. They form dynamic, polydisperse oligomers whose size and composition can change in response to phosphorylation, temperature, and other signals. This structural plasticity is linked to variations in chaperone activity and client specificity.

Localization and regulation vary by organism and tissue. sHSPs are found in the cytosol and various organelles, including mitochondria and chloroplasts in plants. In animals, well-studied members include HSPB1 (Hsp27) and HSPB5 (αB-crystallin). Expression is commonly induced by heat shock factor 1 (HSF1) and modulated by signaling pathways such as p38 MAPK, which can alter oligomer size and activity through phosphorylation.

Functions and clinical relevance extend beyond stress protection. sHSPs participate in protein quality control during normal physiology and aging, influence apoptosis, and contribute to cytoskeletal integrity and cell signaling. Mutations in sHSP genes are linked to diseases such as cataracts (HSPB4/HSPB5), myopathies, and distal hereditary neuropathies, underscoring their importance in cellular homeostasis. Evolutionarily, sHSPs are highly conserved, with bacterial IbpA/B as related relatives, reflecting their fundamental role in proteostasis.