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Small heat shock protein speciation: novel non-canonical 44 kDa HspB5-related protein species in rat and human tissues

Item Type:Article
Title:Small heat shock protein speciation: novel non-canonical 44 kDa HspB5-related protein species in rat and human tissues
Creators Name:Benndorf, R., Gilmont, R.R., Hirano, S., Ransom, R.F., Jungblut, P.R., Bommer, M., Goldman, J.E. and Welsh, M.J.
Abstract:When analyzing small stress proteins of rat and human tissues by electrophoretic methods followed by western blotting, and using the anti-HspB1/anti-HspB5 antibody clone 8A7, we unexpectedly found a protein with a molecular mass of ~44 kDa. On two-dimensional gels, this protein resolved into four distinct species. Electrophoretic and immunological evidence suggests that this 44 kDa protein is a derivative of HspB5, most likely a covalently linked HspB5 dimer. This HspB5-like 44 kDa protein (HspB5L-P44) is particularly abundant in rat heart, brain, and renal cortex and glomeruli. HspB5L-P44 was also found in human brains, including those from patients with Alexander disease, a condition distinguished by cerebral accumulation of HspB5. Gray matter of such a patient contained an elevated amount of HspB5L-P44. A spatial model of structurally ordered dimeric HspB5 α-crystallin domains reveals the exposed and adjacent position of the two peptide segments homologous to the HspB1-derived 8A7 antigen determinant peptide (epitope). This explains the observed extraordinary high avidity of the 8A7 antibody towards HspB5L-P44, as opposed to commonly used HspB5-specific antibodies which recognize other epitopes. This scenario also explains the remarkable fact that no previous study reported the existence of HspB5L-P44 species. Exposure of rat endothelial cells to UV light, an oxidative stress condition, temporarily increased HspB5L-P44, suggesting physiological regulation of the dimerization. The existence of HspB5L-P44 supports the protein speciation discourse and fits to the concept of the protein code, according to which the expression of a given gene is reflected only by the complete set of the derived protein species.
Keywords:Protein Modification, Covalently Bonded HspB5 Dimers, HspB1-/HspB5-Specific Antibody Clone 8A7, Protein Speciation, Mammals, Animals, Rats
Source:Cell Stress & Chaperones
Page Range:813-826
Date:September 2018
Official Publication:https://doi.org/10.1007/s12192-018-0890-5
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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