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Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-tooth neuropathy

Leonardo Almeida-Souza, Sofie Goethals, Vicky de Winter, Ines Dierick, Rodrigo Gallardo, Joost Van Durme, Joy Irobi, Jan Gettemans UGent, Frederic Rousseau, Joost Schymkowitz, et al. (2010) JOURNAL OF BIOLOGICAL CHEMISTRY. 285(17). p.12778-12786
abstract
Small heat shock proteins are molecular chaperones capable of maintaining denatured proteins in a folding-competent state. We have previously shown that missense mutations in the small heat shock protein HSPB1 (HSP27) cause distal hereditary motor neuropathy and axonal Charcot-Marie-Tooth disease. Here we investigated the biochemical consequences of HSPB1 mutations that are known to cause peripheral neuropathy. In contrast to other chaperonopathies, our results revealed that particular HSPB1 mutations presented higher chaperone activity compared with wild type. Hyperactivation of HSPB1 was accompanied by a change from its wild-type dimeric state to a monomer without dissociation of the 24-meric state. Purification of protein complexes from wild-type and HSPB1 mutants showed that the hyperactive isoforms also presented enhanced binding to client proteins. Furthermore, we show that the wildtype HSPB1 protein undergoes monomerization during heat-shock activation, strongly suggesting that the monomer is the active form of the HSPB1 protein.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
MUTATION, ALPHA-CRYSTALLIN DOMAIN, SUBUNIT INTERACTIONS, A-CRYSTALLIN, IN-VIVO, DISSOCIATION, HSP27, HEAT-SHOCK-PROTEIN, B-CRYSTALLIN, CHAPERONE ACTIVITY
journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
J. Biol. Chem.
volume
285
issue
17
pages
12778 - 12786
Web of Science type
Article
Web of Science id
000276787800036
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
5.328 (2010)
JCR rank
50/284 (2010)
JCR quartile
1 (2010)
ISSN
0021-9258
DOI
10.1074/jbc.M109.082644
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
943547
handle
http://hdl.handle.net/1854/LU-943547
date created
2010-05-06 11:42:28
date last changed
2016-12-19 15:47:15
@article{943547,
  abstract     = {Small heat shock proteins are molecular chaperones capable of maintaining denatured proteins in a folding-competent state. We have previously shown that missense mutations in the small heat shock protein HSPB1 (HSP27) cause distal hereditary motor neuropathy and axonal Charcot-Marie-Tooth disease. Here we investigated the biochemical consequences of HSPB1 mutations that are known to cause peripheral neuropathy. In contrast to other chaperonopathies, our results revealed that particular HSPB1 mutations presented higher chaperone activity compared with wild type. Hyperactivation of HSPB1 was accompanied by a change from its wild-type dimeric state to a monomer without dissociation of the 24-meric state. Purification of protein complexes from wild-type and HSPB1 mutants showed that the hyperactive isoforms also presented enhanced binding to client proteins. Furthermore, we show that the wildtype HSPB1 protein undergoes monomerization during heat-shock activation, strongly suggesting that the monomer is the active form of the HSPB1 protein.},
  author       = {Almeida-Souza, Leonardo and Goethals, Sofie and de Winter, Vicky and Dierick, Ines and Gallardo, Rodrigo and Van Durme, Joost and Irobi, Joy and Gettemans, Jan and Rousseau, Frederic and Schymkowitz, Joost and Timmerman, Vincent and Janssens, Sophie},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keyword      = {MUTATION,ALPHA-CRYSTALLIN DOMAIN,SUBUNIT INTERACTIONS,A-CRYSTALLIN,IN-VIVO,DISSOCIATION,HSP27,HEAT-SHOCK-PROTEIN,B-CRYSTALLIN,CHAPERONE ACTIVITY},
  language     = {eng},
  number       = {17},
  pages        = {12778--12786},
  title        = {Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-tooth neuropathy},
  url          = {http://dx.doi.org/10.1074/jbc.M109.082644},
  volume       = {285},
  year         = {2010},
}

Chicago
Almeida-Souza, Leonardo, Sofie Goethals, Vicky de Winter, Ines Dierick, Rodrigo Gallardo, Joost Van Durme, Joy Irobi, et al. 2010. “Increased Monomerization of Mutant HSPB1 Leads to Protein Hyperactivity in Charcot-Marie-tooth Neuropathy.” Journal of Biological Chemistry 285 (17): 12778–12786.
APA
Almeida-Souza, L., Goethals, S., de Winter, V., Dierick, I., Gallardo, R., Van Durme, J., Irobi, J., et al. (2010). Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-tooth neuropathy. JOURNAL OF BIOLOGICAL CHEMISTRY, 285(17), 12778–12786.
Vancouver
1.
Almeida-Souza L, Goethals S, de Winter V, Dierick I, Gallardo R, Van Durme J, et al. Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-tooth neuropathy. JOURNAL OF BIOLOGICAL CHEMISTRY. 2010;285(17):12778–86.
MLA
Almeida-Souza, Leonardo, Sofie Goethals, Vicky de Winter, et al. “Increased Monomerization of Mutant HSPB1 Leads to Protein Hyperactivity in Charcot-Marie-tooth Neuropathy.” JOURNAL OF BIOLOGICAL CHEMISTRY 285.17 (2010): 12778–12786. Print.