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Proteins. 2015 Nov;83(11):2039-51. doi: 10.1002/prot.24921. Epub 2015 Sep 22.

Sucrose prevents protein fibrillation through compaction of the tertiary structure but hardly affects the secondary structure.

Author information

1
Centre for Biomedical Research (CBMR), University of Algarve, Campus of Gambelas, Faro, 8005-139, Portugal.
2
Instituto De Medicina Molecular, Faculdade De Medicina Da Universidade De Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, Lisboa, 1649-028, Portugal.
3
Department of Biomedicine, Aarhus University, Aarhus C, DK-8000, Denmark.
4
Department of Molecular Biology and Genetics, Aarhus University, iNANO (Interdisciplinary Nanoscience Centre), Gustav Wieds Vej 14, Aarhus C, 8000, Denmark.
5
Instituto Superior Técnico, Centro De Química Estrutural, Av. Rovisco Pais, Lisboa, 1049-001, Portugal.

Abstract

Amyloid fibers, implicated in a wide range of diseases, are formed when proteins misfold and stick together in long rope-like structures. As a natural mechanism, osmolytes can be used to modulate protein aggregation pathways with no interference with other cellular functions. The osmolyte sucrose delays fibrillation of the ribosomal protein S6 leading to softer and less shaped-defined fibrils. The molecular mechanism used by sucrose to delay S6 fibrillation was studied based on the two-state unfolding kinetics of the secondary and tertiary structures. It was concluded that the delay in S6 fibrillation results from stabilization and compaction of the slightly expanded tertiary native structure formed under fibrillation conditions. Interestingly, this compaction extends to almost all S6 tertiary structure but hardly affects its secondary structure. The part of the S6 tertiary structure that suffered more compaction by sucrose is known to be the first part to unfold, indicating that the native S6 has entered the unfolding pathway under fibrillation conditions.

KEYWORDS:

S6 protein; osmolytes; protein fibrillation

PMID:
26344410
DOI:
10.1002/prot.24921
[Indexed for MEDLINE]

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