S3-02-03: Targeting protein-protein interactions in heat shock protein 70 (Hsp70) to treat neurodegenerative disease

2013 ◽  
Vol 9 ◽  
pp. P512-P512
Author(s):  
Jason Gestwicki
2021 ◽  
Author(s):  
Oleta T Johnson ◽  
Cory M Nadel ◽  
Emma C Carroll ◽  
Taylor Arhar ◽  
Jason E Gestwicki

Chaperones of the heat shock protein 70 (Hsp70) family engage in protein-protein interactions (PPIs) with many co-chaperones. One hotspot for co-chaperone binding is the EEVD motif that is found at the extreme C-terminus of cytoplasmic Hsp70s. This motif is known to bind tetratricopeptide repeat (TPR) domain co-chaperones, such as the E3 ubiquitin ligase CHIP, and Class B J-domain proteins (JDPs), such as DnaJB4. Although complexes between Hsp70-CHIP and Hsp70-DnaJB4 are both important for chaperone functions, the molecular determinants that dictate the competition between these co-chaperones are not clear. Using a collection of EEVD-derived peptides, we find that DnaJB4 binds to the IEEVD motif of Hsp70s, but not the related MEEVD motif of cytoplasmic Hsp90s. Then, we explored which residues are critical for binding to CHIP and DnaJB4, revealing that they rely on some shared features of the IEEVD motif, such as the C-terminal carboxylate. However, they also had unique preferences, especially at the isoleucine position. Finally, we observed a functionally important role for competition between CHIP and DnaJB4 in vitro, as DnaJB4 can limit the ubiquitination activity of the Hsp70-CHIP complex, while CHIP suppresses the chaperone activities of Hsp70-DnaJB4. Together, these results suggest that the EEVD motif has evolved to support diverse PPIs, such that competition between co-chaperones could help guide whether Hsp70-bound proteins are folded or degraded.


2018 ◽  
Vol 13 (11) ◽  
pp. 3142-3152 ◽  
Author(s):  
Silvia Rinaldi ◽  
Victoria A. Assimon ◽  
Zapporah T. Young ◽  
Giulia Morra ◽  
Hao Shao ◽  
...  

2018 ◽  
Vol 61 (14) ◽  
pp. 6163-6177 ◽  
Author(s):  
Hao Shao ◽  
Xiaokai Li ◽  
Michael A. Moses ◽  
Luke A. Gilbert ◽  
Chakrapani Kalyanaraman ◽  
...  

2000 ◽  
Vol 275 (41) ◽  
pp. 31682-31688 ◽  
Author(s):  
Jeongwoo Kang ◽  
Taeho Kim ◽  
Young-Gyu Ko ◽  
Seung Bae Rho ◽  
Sang Gyu Park ◽  
...  

2021 ◽  
Vol 82 (1) ◽  
Author(s):  
A. B. Sikiru ◽  
O. J. Makinde ◽  
E. Opoola ◽  
S. K. Omotugba ◽  
A. R. Musa

Abstract Background The heat shock protein-70 (HSP70) is a protein associated with response and adaptation to stress, as well as protection of the cells against thermal and oxidative stress in animals. It is an evolutionarily conserved protein, but its expression has been reportedly varied. Therefore, this study implemented computational analyses of the amino acid sequences of this gene for a better understanding of the evolutionary and protein interactions variations associated with the gene to facilitate its exploitation for the breeding of animals with increasing adaptation to heat stress. Results The result showed that there is a wide evolutionary distance between humans and the selected farm animals studied but elegans shared a common evolutionary relationship with the farm animals. The sequence identity analysis returned exact matches among the sequences as minimum = 8.09%, maximum = 98.58%, and mean ± SD = 71.03 ± 26.3% across all the species, while the sequence similarities resemblance among the sequences were minimum = 16.49%, maximum = 100%, and mean ± SD = 78.99 ± 24.39%. The global block substitution matrix (BLOSUM62) analysis returned minimum = 0.18, maximum = 0.98, and mean ± SD = 0.62 ± 0.34. The analysis of the molecular weight of the protein sequences returned minimum = 5.70 kDa, maximum = 6.41 kDa, mean = 6.28 kDa, and standard deviation 0.17 kDa, and the isoelectric point of the protein sequences was minimum = 4.55, maximum = 7.17, mean = 5.56, and standard deviation = 0.65 while the hydrophobicity of the protein sequences were minimum = 45.20 kcal/mol, maximum = 53.02 kcal/mol, mean = 47.81 kcal/mol, and standard deviation = 1.85 kcal/mol. Conclusion The outcomes of the computational analyses led to the conclusion that variations exist in the conservations of amino acid residues of the gene in the studied farm and non-farm animals, and this is responsible for the differences and similarities in the expression of the HSP70 gene in different animals. It was also concluded that elegans are suitable model that could be exploited for a better understanding of response and adaptation to heat stress in duck, chicken, cattle, sheep, and goat when focusing on regulation and expression of heat shock protein gene 70 (HSP70).


1994 ◽  
Vol 269 (15) ◽  
pp. 11155-11161
Author(s):  
M.J. Czar ◽  
J.K. Owens-Grillo ◽  
K.D. Dittmar ◽  
K.A. Hutchison ◽  
A.M. Zacharek ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A152-A152
Author(s):  
H SUZUKI ◽  
S NAGAHASHI ◽  
M MIYAZAWA ◽  
M MORI ◽  
H NAGATA ◽  
...  

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