Quantitative assessment of chaperone binding to amyloid aggregates identifies specificity of Hsp40 interaction with yeast prion fibrils.

Barbitoff, Yury A; Matveenko, Andrew G; Bondarev, Stanislav A; Maksiutenko, Evgeniia M; Kulikova, Alexandra V; Zhouravleva, Galina A

Barbitoff, Yury A; Matveenko, Andrew G; Bondarev, Stanislav A; Maksiutenko, Evgeniia M; Kulikova, Alexandra V; Zhouravleva, Galina A.

Afiliación

Barbitoff YA; Department of Genetics and Biotechnology, St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia.
Matveenko AG; Department of Genetics and Biotechnology, St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia.
Bondarev SA; Department of Genetics and Biotechnology, St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia.
Maksiutenko EM; Laboratory of Amyloid Biology, St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia.
Kulikova AV; Department of Genetics and Biotechnology, St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia.
Zhouravleva GA; St. Petersburg Branch, Vavilov Institute of General Genetics, Russian Academy of Sciences, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia.

FEMS Yeast Res ; 20(4)2020 06 01.

Article en En | MEDLINE | ID: mdl-32379306

RESUMEN

Yeast self-perpetuating protein aggregates (yeast prions) provide a framework to investigate the interaction of misfolded proteins with the protein quality control machinery. The major component of this system that facilitates propagation of all known yeast amyloid prions is the Hsp104 chaperone that catalyzes fibril fragmentation. Overproduction of Hsp104 cures some yeast prions via a fragmentation-independent mechanism. Importantly, major cytosolic chaperones of the Hsp40 group, Sis1 and Ydj1, oppositely affect yeast prion propagation, and are capable of stimulating different activities of Hsp104. In this work, we developed a quantitative method to investigate the Hsp40 binding to amyloid aggregates. We demonstrate that Sis1 binds fibrils formed by the Sup35NM protein with higher affinity compared to Ydj1. Moreover, the interaction of Sis1 with the fibrils formed by the other yeast prion protein, Rnq1, is orders of magnitude weaker. We show that the deletion of the dimerization domain of Sis1 (crucial for the curing of [PSI+] by excess Hsp104) decreases its affinity to both Sup35NM and Rnq1 fibrils. Taken together, these results suggest that tight binding of Hsp40 to the amyloid fibrils is likely to enhance aggregate malpartition instead of fibril fragmentation.

Asunto(s)

Amiloide/metabolismo; Proteínas Fúngicas/metabolismo; Proteínas del Choque Térmico HSP40/metabolismo; Chaperonas Moleculares/metabolismo; Priones/metabolismo; Levaduras/metabolismo; Amiloide/análisis; Amiloide/genética; Proteínas Fúngicas/genética; Proteínas del Choque Térmico HSP40/genética; Chaperonas Moleculares/análisis; Chaperonas Moleculares/genética; Unión Proteica; Transporte de Proteínas; Levaduras/química; Levaduras/genética

Palabras clave

Hsp40; Sis1; aggregate binding; protein quality control; yeast prion

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Levaduras / Priones / Proteínas Fúngicas / Chaperonas Moleculares / Proteínas del Choque Térmico HSP40 / Amiloide Idioma: En Revista: FEMS Yeast Res Asunto de la revista: MICROBIOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido

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