Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein
The synucleins are a family of natively unstructured proteins consisting of α-, β-, and γ-synuclein which are primarily expressed in neurons. They have been linked to a wide variety of pathologies, including neurological disorders, such as Parkinson’s disease (α-synuclein) and dementia with Lewy bod...
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| Format: | Online |
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904966/ |
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pubmed-39049662014-01-31 Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein Ducas, Vanessa C. Rhoades, Elizabeth Research Article The synucleins are a family of natively unstructured proteins consisting of α-, β-, and γ-synuclein which are primarily expressed in neurons. They have been linked to a wide variety of pathologies, including neurological disorders, such as Parkinson’s disease (α-synuclein) and dementia with Lewy bodies (α- and β-synuclein), as well as various types of cancers (γ-synuclein). Self-association is a key pathological feature of many of these disorders, with α-synuclein having the highest propensity to form aggregates, while β-synuclein is the least prone. Here, we used a combination of fluorescence correlation spectroscopy and single molecule Förster resonance energy transfer to compare the intrinsic dynamics of different regions of all three synuclein proteins to investigate any correlation with putative functional or dysfunctional interactions. Despite a relatively high degree of sequence homology, we find that individual regions sample a broad range of diffusion coefficients, differing by almost a factor of four. At low pH, a condition that accelerates aggregation of α-synuclein, on average smaller diffusion coefficients are measured, supporting a hypothesis that slower intrachain dynamics may be correlated with self-association. Moreover, there is a surprising inverse correlation between dynamics and bulkiness of the segments. Aside from this observation, we could not discern any clear relationship between the physico-chemical properties of the constructs and their intrinsic dynamics. This work suggests that while protein dynamics may play a role in modulating self-association or interactions with other binding partners, other factors, particularly the local cellular environment, may be more important. Public Library of Science 2014-01-28 /pmc/articles/PMC3904966/ /pubmed/24489820 http://dx.doi.org/10.1371/journal.pone.0086983 Text en © 2014 Ducas, Rhoades http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Ducas, Vanessa C. Rhoades, Elizabeth |
| spellingShingle |
Ducas, Vanessa C. Rhoades, Elizabeth Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein |
| author_facet |
Ducas, Vanessa C. Rhoades, Elizabeth |
| author_sort |
Ducas, Vanessa C. |
| title |
Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein |
| title_short |
Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein |
| title_full |
Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein |
| title_fullStr |
Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein |
| title_full_unstemmed |
Investigation of Intramolecular Dynamics and Conformations of α-, β- and γ-Synuclein |
| title_sort |
investigation of intramolecular dynamics and conformations of α-, β- and γ-synuclein |
| description |
The synucleins are a family of natively unstructured proteins consisting of α-, β-, and γ-synuclein which are primarily expressed in neurons. They have been linked to a wide variety of pathologies, including neurological disorders, such as Parkinson’s disease (α-synuclein) and dementia with Lewy bodies (α- and β-synuclein), as well as various types of cancers (γ-synuclein). Self-association is a key pathological feature of many of these disorders, with α-synuclein having the highest propensity to form aggregates, while β-synuclein is the least prone. Here, we used a combination of fluorescence correlation spectroscopy and single molecule Förster resonance energy transfer to compare the intrinsic dynamics of different regions of all three synuclein proteins to investigate any correlation with putative functional or dysfunctional interactions. Despite a relatively high degree of sequence homology, we find that individual regions sample a broad range of diffusion coefficients, differing by almost a factor of four. At low pH, a condition that accelerates aggregation of α-synuclein, on average smaller diffusion coefficients are measured, supporting a hypothesis that slower intrachain dynamics may be correlated with self-association. Moreover, there is a surprising inverse correlation between dynamics and bulkiness of the segments. Aside from this observation, we could not discern any clear relationship between the physico-chemical properties of the constructs and their intrinsic dynamics. This work suggests that while protein dynamics may play a role in modulating self-association or interactions with other binding partners, other factors, particularly the local cellular environment, may be more important. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904966/ |
| _version_ |
1612052136736063488 |