HSPB4HSPB5

HSPB4 and HSPB5 are small heat shock proteins in the HSPB family, also known as alpha-crystallin A and alpha-crystallin B, respectively. They function as molecular chaperones that prevent the aggregation of unfolded proteins in a ATP-independent manner and help maintain protein homeostasis under stress. In vertebrates, these proteins are highly conserved and can form dynamic oligomeric complexes, including heterooligomers, which enhances their chaperone efficiency.

Gene and tissue distribution: HSPB4 encodes the alpha-crystallin A chain, which is predominantly expressed in the lens of the eye where it contributes to the transparency and refractive properties of the lens. HSPB5 encodes the alpha-crystallin B chain, which is more broadly expressed, with notable levels in the heart, skeletal muscle, brain, and retina. Both proteins contain an alpha-crystallin domain and variable N- and C-terminal regions that influence oligomerization and chaperone activity. Phosphorylation and other post-translational modifications can modulate their function and interactions.

Function and interactions: As chaperones, HSPB4 and HSPB5 stabilize partially unfolded proteins, preventing irreversible aggregation and assisting in the refolding process indirectly. They interact with a range of substrates, including cytoskeletal proteins such as desmin and vimentin, and can influence cellular stress responses and cytoskeletal integrity. Their ability to form heterooligomers suggests cooperative roles in maintaining proteostasis across tissues.

Clinical relevance: Mutations in the CRYAA (HSPB4) and CRYAB (HSPB5) genes are associated with ocular cataracts, cardiomyopathy, and desmin-related myopathies. Such mutations can disrupt chaperone function, protein interactions, or oligomerization, contributing to tissue-specific pathologies. Research continues to explore their roles in aging, neuroprotection, and potential therapeutic applications.

See also: small heat shock proteins, CRYAA, CRYAB, cataract.