Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics
Yeast prions are self-templating protein-based mechanisms of inheritance whose conformational changes lead to the acquisition of diverse new phenotypes. The best studied of these is the prion domain (NM) of Sup35, which forms an amyloid that can adopt several distinct conformations (strains) that pr...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/104011 https://orcid.org/0000-0003-1589-832X https://orcid.org/0000-0003-1307-882X |
| _version_ | 1826199300489609216 |
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| author | Frederick, Kendra K. Debelouchina, Galia Tzvetanova Kayatekin, Can Dorminy, Tea Jacavone, Angela Griffin, Robert Guy Lindquist, Susan |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Frederick, Kendra K. Debelouchina, Galia Tzvetanova Kayatekin, Can Dorminy, Tea Jacavone, Angela Griffin, Robert Guy Lindquist, Susan |
| author_sort | Frederick, Kendra K. |
| collection | MIT |
| description | Yeast prions are self-templating protein-based mechanisms of inheritance whose conformational changes lead to the acquisition of diverse new phenotypes. The best studied of these is the prion domain (NM) of Sup35, which forms an amyloid that can adopt several distinct conformations (strains) that produce distinct phenotypes. Using magic-angle spinning nuclear magnetic resonance spectroscopy, we provide a detailed look at the dynamic properties of these forms over a broad range of timescales. We establish that different prion strains have distinct amyloid structures, with many side chains in different chemical environments. Surprisingly, the prion strain with a larger fraction of rigid residues also has a larger fraction of highly mobile residues. Differences in mobility correlate with differences in interaction with the prion-partitioning factor Hsp104 in vivo, perhaps explaining strain-specific differences in inheritance. |
| first_indexed | 2024-09-23T11:17:59Z |
| format | Article |
| id | mit-1721.1/104011 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:17:59Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1040112022-09-27T18:33:00Z Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics Frederick, Kendra K. Debelouchina, Galia Tzvetanova Kayatekin, Can Dorminy, Tea Jacavone, Angela Griffin, Robert Guy Lindquist, Susan Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Whitehead Institute for Biomedical Research Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology) Debelouchina, Galia Tzvetanova Dorminy, Tea Jacavone, Angela Griffin, Robert Guy Lindquist, Susan Yeast prions are self-templating protein-based mechanisms of inheritance whose conformational changes lead to the acquisition of diverse new phenotypes. The best studied of these is the prion domain (NM) of Sup35, which forms an amyloid that can adopt several distinct conformations (strains) that produce distinct phenotypes. Using magic-angle spinning nuclear magnetic resonance spectroscopy, we provide a detailed look at the dynamic properties of these forms over a broad range of timescales. We establish that different prion strains have distinct amyloid structures, with many side chains in different chemical environments. Surprisingly, the prion strain with a larger fraction of rigid residues also has a larger fraction of highly mobile residues. Differences in mobility correlate with differences in interaction with the prion-partitioning factor Hsp104 in vivo, perhaps explaining strain-specific differences in inheritance. Howard Hughes Medical Institute (Investigator) Howard Hughes Medical Institute (HHMI fellow of the Life Science Research Foundation) National Institutes of Health (U.S.) (NIH grant GM025874) National Institutes of Health (U.S.) (NIH grant EB003151) National Institutes of Health (U.S.) (NIH grant EB002026) 2016-08-26T14:02:07Z 2016-08-26T14:02:07Z 2014-01 2013-11 Article http://purl.org/eprint/type/JournalArticle 10745521 http://hdl.handle.net/1721.1/104011 Frederick, Kendra K., Galia T. Debelouchina, Can Kayatekin, Tea Dorminy, Angela C. Jacavone, Robert G. Griffin, and Susan Lindquist. "Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics." Chemistry & Biology 21:2 (20 February 2014), pp. 295-305. https://orcid.org/0000-0003-1589-832X https://orcid.org/0000-0003-1307-882X en_US http://dx.doi.org/10.1016/j.chembiol.2013.12.013 Chemistry & Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Frederick, Kendra K. Debelouchina, Galia Tzvetanova Kayatekin, Can Dorminy, Tea Jacavone, Angela Griffin, Robert Guy Lindquist, Susan Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics |
| title | Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics |
| title_full | Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics |
| title_fullStr | Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics |
| title_full_unstemmed | Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics |
| title_short | Distinct Prion Strains Are Defined by Amyloid Core Structure and Chaperone Binding Site Dynamics |
| title_sort | distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics |
| url | http://hdl.handle.net/1721.1/104011 https://orcid.org/0000-0003-1589-832X https://orcid.org/0000-0003-1307-882X |
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