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Orientation of α-Sy...
Orientation of α-Synuclein at Negatively Charged Lipid Vesicles: Linear Dichroism Reveals Time-Dependent Changes in Helix Binding Mode
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- Rocha, Sandra, 1975 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Kumar, Ranjeet, 1980 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Nordén, Bengt, 1945 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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visa fler...
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- Wittung Stafshede, Pernilla, 1968 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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visa färre...
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(creator_code:org_t)
- 2021-11-08
- 2021
- Engelska.
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 143:45, s. 18899-18906
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https://research.cha... (primary) (free)
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https://pubs.acs.org...
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https://doi.org/10.1...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- The neuronal protein α-synuclein, linked to Parkinson's disease, binds to negatively charged vesicles adopting a partial α-helix structure, but helix arrangement at the vesicle surface is not fully understood. Using linear dichroism spectroscopy (LD), we study the interaction of monomeric α-synuclein with large unilamellar vesicles of 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS), and 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG) under mild shear flow. The LD data of oriented lipid vesicles show that the long axis of the protein helix is oriented preferentially perpendicular to the membrane normal but deviates from a uniform in-plane distribution. Upon initial binding, a fraction of helices are oriented in the direction of least curvature for all ellipsoid-shaped vesicles at a lipid:protein molar ratio of 100. However, at a lower protein concentration the helices distribute uniformly on DOPS and POPS vesicles. In all cases, the α-synuclein helices rearrange with time (minute time scale) in the shear flow and begin to tilt into the vesicle membrane. Faster reorientation kinetics in the presence of flow suggests that modulation of membrane dynamics, by thermal or shear-dynamic activation, may overcome steric barriers by what may be called "flow catalysis".
Ämnesord
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
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