Title: Increased Monomerization of Mutant HSPB1 Leads to Protein Hyperactivity in Charcot-Marie-Tooth Neuropathy
Authors: Almeida-Souza, Leonardo ×
Goethals, Sofie
de Winter, Vicky
Dierick, Ines
Gallardo, Rodrigo
Van Durme, Joost
Irobi, Joy
Gettemans, Jan
Rousseau, Frederic
Schymkowitz, Joost
Timmerman, Vincent
Janssens, Sophie #
Issue Date: Apr-2010
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:285 issue:17 pages: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.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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