Mutations linked to neurological disease enhance self-association of low-complexity protein sequences
| العنوان: | Mutations linked to neurological disease enhance self-association of low-complexity protein sequences |
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| المؤلفون: | Xiaoming Zhou, Lily Sumrow, Kyuto Tashiro, Lillian Sutherland, Daifei Liu, Tian Qin, Masato Kato, Glen Liszczak, Steven L. McKnight |
| المصدر: | Science |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | DNA-Binding Proteins, Protein Folding, Multidisciplinary, Protein Domains, Alzheimer Disease, Charcot-Marie-Tooth Disease, Protein Stability, Frontotemporal Dementia, Mutation, Missense, Humans, Cells, Cultured, Article |
| الوصف: | Protein domains of low sequence complexity do not fold into stable, three-dimensional structures. Nevertheless, proteins with these sequences assist in many aspects of cell organization, including assembly of nuclear and cytoplasmic structures not surrounded by membranes. The dynamic nature of these cellular assemblies is caused by the ability of low-complexity domains (LCDs) to transiently self-associate through labile, cross-β structures. Mechanistic studies useful for the study of LCD self-association have evolved over the past decade in the form of simple assays of phase separation. Here, we have used such assays to demonstrate that the interactions responsible for LCD self-association can be dictated by labile protein structures poised close to equilibrium between the folded and unfolded states. Furthermore, missense mutations causing Charcot-Marie-Tooth disease, frontotemporal dementia, and Alzheimer’s disease manifest their pathophysiology in vitro and in cultured cell systems by enhancing the stability of otherwise labile molecular structures formed upon LCD self-association. |
| تدمد: | 1095-9203 0036-8075 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8afce5ac3de7d9dcb55e1df651f38edTest https://doi.org/10.1126/science.abn5582Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a8afce5ac3de7d9dcb55e1df651f38ed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10959203 00368075 |
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