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Characterization of human small heat shock protein HspB1 that carries C-terminal domain mutations associated with hereditary motor neuron diseasesстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 2 апреля 2015 г.
- Авторы: Chalova Anna S., Sudnitsyna Maria V., Strelkov Sergei V., Gusev Nikolai B.
- Журнал: Biochimica et Biophysica Acta - Proteins and Proteomics
- Том: 1844
- Номер: 12
- Год издания: 2014
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 2116
- Последняя страница: 2126
- DOI: 10.1016/j.bbapap.2014.09.005
- Аннотация: Physico-chemical properties of four mutants (T164A, T180I, P182S and R188W) of human small heat shock protein HspB1 (Hsp27) associated with neurodegenerative diseases were analyzed by means of fluorescence spectroscopy, dynamic light scattering, size-exclusion chromatography and measurement of chaperone-like activity. Mutation T164A was accompanied by destabilization of the quaternary structure and decrease of thermal stability without any significant changes of chaperone-like activity. Mutations T180I and P182S are adjacent or within the conserved C-terminal motif IPI/V. Replacement T180⇒I leading to the formation of hydrophobic cluster consisting of three Ile produced small increase of thermal stability without changes of chaperone-like activity. Mutation P182S induced the formation of metastable large oligomers of HspB1 with apparent molecular weight of more than 1000kDa. Oligomers of P182S have very low thermal stability and undergo irreversible aggregation at low temperature. The P182S mutant forms mixed oligomers with the wild type HspB1 and the properties of these mixed oligomers are intermediate between those of the wild type HspB1 and its mutant. Mutation R188W did not significantly affect quaternary structure or thermal stability of HspB1, but was accompanied by a pronounced decrease of its chaperone-like activity. All mutations analyzed are associated with hereditary motor neuropathies or Charcot-Marie-Tooth disease type 2; however, molecular mechanisms underlying pathological effects are specific for each of these mutants.
- Добавил в систему: Гусев Николай Борисович