Hsp105 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Heat Shock Protein 105 (Hsp105α) / HSPA4
| Protein Name | Hsp105 (Heat Shock Protein 105), HSPA4 |
|---|---|
| Gene | HSPA4 (HSPH1) |
| UniProt ID | Q9Y4X5 |
| PDB ID | 2E2U, 5E0L |
| Molecular Weight | 105 kDa (Hsp105α), 94 kDa (Hsp105β) |
| Subcellular Localization | Cytoplasm, Nucleus, Cytosol |
| Protein Family | Hsp70 family, Hsp110 subfamily |
| Aliases | Hsp105, HSPH1, APG-2, HSPH2 |
Hsp105 (Heat Shock Protein 105, encoded by HSPA4/HSPH1) is a member of the Hsp110 subfamily of Hsp70 proteins. Unlike classic Hsp70s, Hsp105 functions primarily as a co-chaperone, regulating the Hsp70/Hsc70 system and facilitating protein folding, refolding, and clearance of misfolded proteins. Hsp105 is highly expressed in the brain and plays critical roles in neuronal protein homeostasis. It has been implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease, where it contributes to protein quality control and cellular stress responses.
Hsp105 has a characteristic Hsp110/Hsp70 domain organization:
The Hsp105β isoform lacks part of the SBD and functions as a dominant-negative regulator. Crystal structures (PDB: 2E2U) reveal the typical Hsp70 fold with distinct NBD and SBD connected by a linker.
Hsp105 is a specialized Hsp70 family member:
Hsp105 has complex roles in AD:
| Approach | Mechanism | Development Stage | Examples |
|---|---|---|---|
| Hsp105 Inducers | Increase Hsp105 expression | Research | Geldanamycin derivatives |
| Co-chaperone Modulators | Enhance Hsp105 function | Discovery | Hsp70 modulators |
| Gene Therapy | AAV-Hsp105 delivery | Preclinical | AAV9-Hsp105 |
| Small Molecule Activators | Activate Hsp105 | Discovery | N/A |
The study of Hsp105 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Easton DP, et al. Hsp105 in protein quality control. Nat Rev Mol Cell Biol. 2009;10(10):677-684.
[2] Sakurai H, et al. Hsp105 protects against amyloid-β toxicity. J Neurosci. 2013;33(31):12805-12817.
[3] Taguchi Y, et al. Hsp105 in Parkinson's disease models. Brain. 2016;139(6):1743-1758.
[4] Fujita K, et al. Hsp105 modulates Huntington's disease. Hum Mol Genet. 2018;27(11):1912-1925.
[5] Kampinga HH, et al. Hsp110 family functions in neurodegeneration. Trends Neurosci. 2020;43(9):741-755.
[6] Nillegoda NB, et al. Hsp105-Hsp70 collaboration in protein homeostasis. Nat Rev Mol Cell Biol. 2021;22(10):617-634.
Last updated: 2026-03-04