REVIEW: Mutations of Small Heat Shock Proteins and Human Congenital Diseases

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P. N. Datskevich^#, V. V. Nefedova^#, M. V. Sudnitsyna, and N. B. Gusev^*

Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; E-mail: NBGusev@mail.ru

^# Contributed equally to this paper.

^* To whom correspondence should be addressed.

Received July 16, 2012

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The structure and properties of different members of a large family of small heat shock proteins (sHsp) playing an important role in cell homeostasis are described. Participation of the N-terminal domain in formation of large oligomers and chaperone activity of sHsp is analyzed. The structure of the α-crystallin domain of sHsp is characterized and the role of this domain in sHsp dimerization and chaperone activity is discussed. The properties of the C-terminal region of sHsp are described, and its participation in formation of large oligomers and chaperone activity are analyzed. The data from the literature on HspB1 and HspB3 mutations are presented, and involvement of these mutations in development of certain neurodegenerative diseases is discussed. Mutations of HspB4 are described and data on involvement of these mutations in development of cataract are presented. Multiple effects of HspB5 mutations are analyzed, and data are presented indicating that mutations of this protein are accompanied by development of different congenital diseases, such as cataract and different types of myopathies. The data on HspB6 and HspB8 mutations are presented, and feasible effects of these mutations on proteins structure are analyzed. Probable mechanisms underlying sHsp mutation-induced development of different congenital diseases are discussed.

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KEY WORDS: small heat shock proteins, mutation, human congenital diseases, phosphorylation

DOI: 10.1134/S0006297912130081

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