On α-synuclein cooperativity in lipidic membranes binding
(2022) KEMP30 20221Department of Chemistry
- Abstract
- α-Synuclein is an intrinsically disordered protein implied in still not-well-known healthy function and also found as the main component of aggregates in Lewy bodies and Lewy neurites, hallmarks of the Parkinson’s disease. In both of cases, the interaction with lipid membranes is crucial. In this study we propose the investigation of the interaction between α-Synuclein and model systems made of DOPC:DOPS (7:3 molar ratio) in a wide range of condition in order to evaluate the cooperativity of α-Synuclein in lipid membranes binding. Cooperativity is a widespread concept in biochemistry since it is related to many metabolic pathways, signaling and transport processes. In a cooperative event the binding of one molecule onto a surface enhances... (More)
- α-Synuclein is an intrinsically disordered protein implied in still not-well-known healthy function and also found as the main component of aggregates in Lewy bodies and Lewy neurites, hallmarks of the Parkinson’s disease. In both of cases, the interaction with lipid membranes is crucial. In this study we propose the investigation of the interaction between α-Synuclein and model systems made of DOPC:DOPS (7:3 molar ratio) in a wide range of condition in order to evaluate the cooperativity of α-Synuclein in lipid membranes binding. Cooperativity is a widespread concept in biochemistry since it is related to many metabolic pathways, signaling and transport processes. In a cooperative event the binding of one molecule onto a surface enhances the affinity of the next binding event on the same surface, resulting in a non-random distribution. Cooperative binding of α-Synuclein in lipid membranes was already found for the same system in MES buffer at pH 5.5. Here we systematically changed parameters such as pH, ionic strength and amino acidic sequence in order to evaluate the cooperativity, by means of confocal laser scanning microscopy, circular dichroism and fluorescence cross correlation spectroscopy. Both small unilamellar vesicles as well as giant unilamellar vesicles were used as model systems. The binding was observed for all the conditions investigated and, in addition, for some of them fluorescence cross correlation spectroscopy and confocal microscopy proof a positive cooperative binding in excess of vesicles. (Less)
- Popular Abstract
- All biochemical reactions in our bodies are finely controlled in order to guarantee its healthy function. When this does not happen, pathologies can occur. Proteins and lipids are the building blocks of our body so that a mis-regulation in their interaction can lead to the onset of severe diseases.
In this study the focus was given to α-Synuclein and its interaction with model systems act to mime lipid membranes. α-Synuclein is a neuronal protein localized in vivo in synapses where signaling, of electrical or chemical nature, happens. Although the role of α-Synuclein is not fully understood, it has been hypothesized that this protein may take part to the synaptic plasticity, to neurotransmitter release and to other important event implied... (More) - All biochemical reactions in our bodies are finely controlled in order to guarantee its healthy function. When this does not happen, pathologies can occur. Proteins and lipids are the building blocks of our body so that a mis-regulation in their interaction can lead to the onset of severe diseases.
In this study the focus was given to α-Synuclein and its interaction with model systems act to mime lipid membranes. α-Synuclein is a neuronal protein localized in vivo in synapses where signaling, of electrical or chemical nature, happens. Although the role of α-Synuclein is not fully understood, it has been hypothesized that this protein may take part to the synaptic plasticity, to neurotransmitter release and to other important event implied in the maintenance of cells health. On the other hand, excess of α-Synuclein cause the formation of insoluble aggregates which are hallmarks of aberrant neurodegenerative disease. Parkinson’s disease is characterized by the presence of Lewy Bodies and Lewy Neurites which are mainly composed of α-Synuclein as well as lipids.
In this work, we investigated the interaction between α-Synuclein and lipid membranes in a wide range of condition. In addition, this study was born in the wake of precedent findings made on the same system in fixed conditions. Here we systematically varied physical chemical conditions such as pH, ionic strength, and amino acidic sequence. We have found that the binding of α-Synuclein with lipid membranes is cooperative under some conditions just as it has been proven in precedent studies in different conditions.
Cooperativity is a common key-word in the biological world. Many different biochemical pathways are characterized by this mood of binding. In a cooperative event we expect that the binding of the first molecule enhance the affinity of binding of another molecule on the same surface. Translating this to our system, in such conditions, we expect some vesicles to be completely empty and others full of protein.
We believe that this study can be a good starting point to positively contribute to a deeper understanding of mechanism behind both the healthy and the pathologic function of α-Synuclein. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9100729
- author
- Ferrante Carrante, Noemi LU
- supervisor
-
- Emma Sparr LU
- organization
- course
- KEMP30 20221
- year
- 2022
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Physical Chemistry, a-synuclein, Cooperativity
- language
- English
- id
- 9100729
- date added to LUP
- 2022-09-26 11:14:44
- date last changed
- 2022-09-26 11:14:44
@misc{9100729,
abstract = {{α-Synuclein is an intrinsically disordered protein implied in still not-well-known healthy function and also found as the main component of aggregates in Lewy bodies and Lewy neurites, hallmarks of the Parkinson’s disease. In both of cases, the interaction with lipid membranes is crucial. In this study we propose the investigation of the interaction between α-Synuclein and model systems made of DOPC:DOPS (7:3 molar ratio) in a wide range of condition in order to evaluate the cooperativity of α-Synuclein in lipid membranes binding. Cooperativity is a widespread concept in biochemistry since it is related to many metabolic pathways, signaling and transport processes. In a cooperative event the binding of one molecule onto a surface enhances the affinity of the next binding event on the same surface, resulting in a non-random distribution. Cooperative binding of α-Synuclein in lipid membranes was already found for the same system in MES buffer at pH 5.5. Here we systematically changed parameters such as pH, ionic strength and amino acidic sequence in order to evaluate the cooperativity, by means of confocal laser scanning microscopy, circular dichroism and fluorescence cross correlation spectroscopy. Both small unilamellar vesicles as well as giant unilamellar vesicles were used as model systems. The binding was observed for all the conditions investigated and, in addition, for some of them fluorescence cross correlation spectroscopy and confocal microscopy proof a positive cooperative binding in excess of vesicles.}},
author = {{Ferrante Carrante, Noemi}},
language = {{eng}},
note = {{Student Paper}},
title = {{On α-synuclein cooperativity in lipidic membranes binding}},
year = {{2022}},
}