期刊
BIOMOLECULES
卷 12, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/biom12101426
关键词
Dss1; intrinsically disordered protein; IDPs; molecular dynamics; NMR; sequence composition; SAXS
资金
- Novo Nordisk Foundation [NNF18OC0032996]
- Lundbeck Foundation BRAINSTRUC initiative [R155-2015-2666]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [101023654]
- Marie Curie Actions (MSCA) [101023654] Funding Source: Marie Curie Actions (MSCA)
By comparing the effects of aspartate and glutamates in intrinsically disordered proteins, the study found that while the variants support similar function and global dimensions, they differ in binding affinities and population of local transient structural elements, indicating potential roles in functional diversity.
Compared to folded proteins, the sequences of intrinsically disordered proteins (IDPs) are enriched in polar and charged amino acids. Glutamate is one of the most enriched amino acids in IDPs, while the chemically similar amino acid aspartate is less enriched. So far, the underlying functional differences between glutamates and aspartates in IDPs remain poorly understood. In this study, we examine the differential effects of aspartate and glutamates in IDPs by comparing the function and conformational ensemble of glutamate and aspartate variants of the disordered protein Dss1, using a range of assays, including interaction studies, nuclear magnetic resonance spectroscopy, small-angle X-ray scattering and molecular dynamics simulation. First, we analyze the sequences of the rapidly growing database of experimentally verified IDPs (DisProt) and show that glutamate enrichment is not caused by a taxonomy bias in IDPs. From analyses of local and global structural properties as well as cell growth and protein-protein interactions using a model acidic IDP from yeast and three Glu/Asp variants, we find that while the Glu/Asp variants support similar function and global dimensions, the variants differ in their binding affinities and population of local transient structural elements. We speculate that these local structural differences may play roles in functional diversity, where glutamates can support increased helicity, important for folding and binding, while aspartates support extended structures and form helical caps, as well as playing more relevant roles in, e.g., transactivation domains and ion-binding.
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