Related ArticlesSolid-State (13)C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein.
J Mol Biol. 2013 Apr 11;
Authors: Leftin A, Job C, Beyer K, Brown MF
Abstract
Misfolding and aggregation of the intrinsically disordered protein ?-Synuclein (?S) in Lewy body plaques is a characteristic marker of late-stage Parkinson's disease. It is well established that membrane binding is initiated at the N-terminus of the protein and affects biasing of conformational ensembles of ?S. However, little is understood about the effect of ?S on the membrane lipid bilayer. One hypothesis is that intrinsically disordered ?S alters the structural properties of the membrane, thereby stabilizing the bilayer against fusion. Here, we used two-dimensional (13)C separated local-field NMR to study interaction of the wild-type ?S (wt-?S) or its N-terminal (1-25) amino acid sequence (N-?S) with a cholesterol-enriched ternary membrane system. This lipid bilayer mimics cellular raft-like domains in the brain that are proposed to be involved in neuronal membrane fusion. The 2D dipolar-recoupling pulse sequence DROSS was implemented to measure isotropic (13)C chemical shifts and (13)C-(1)H residual dipolar couplings under magic-angle spinning. Site-specific changes in NMR chemical shifts and segmental order parameters indicate that both wt-?S and N-?S bind to the membrane interface and change lipid packing within raft-like membranes. Mean-torque modeling of (13)C-(1)H NMR order parameters shows ?S induces a remarkable thinning of the bilayer (? 6 Å), accompanied by an increase in phospholipid cross-sectional area (? 10 Å(2)). This perturbation is characterized as membrane annealing and entails structural remodeling of the raft-like liquid-ordered phase. We propose this process is implicated in regulation of synaptic membrane fusion that may be altered by aggregation of ?S in Parkinson's disease.
PMID: 23583776 [PubMed - as supplied by publisher]
Solid-State 13C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein
Solid-State 13C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein
Publication date: Available online 11 April 2013
Source:Journal of Molecular Biology</br>
Author(s): Avigdor Leftin , Constantin Job , Klaus Beyer , Michael F. Brown</br>
Misfolding and aggregation of the intrinsically disordered protein ?-Synuclein (?S) in Lewy body plaques is a characteristic marker of late-stage Parkinson’s disease. It is well established that membrane binding is initiated at the N-terminus of the protein and...
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04-11-2013 09:27 PM
[NMR paper] Interactions of lipopolysaccharide with lipid membranes, raft models - a solid state NMR study.
Interactions of lipopolysaccharide with lipid membranes, raft models - a solid state NMR study.
Related Articles Interactions of lipopolysaccharide with lipid membranes, raft models - a solid state NMR study.
Biochim Biophys Acta. 2013 Apr 5;
Authors: Ciesielski F, Griffin DC, Rittig M, Moriyón I, Bonev BB
Abstract
Lipopolysaccharide (LPS) is a major component of the external leaflet of bacterial outer membranes, key pro-inflammatory factor and an important mediator of host-pathogen interactions. In host cells it activates the complement...
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04-10-2013 07:21 PM
Deuterium isotope shifts for backbone 1H, 15N and 13C nuclei in intrinsically disordered protein α-synuclein
Deuterium isotope shifts for backbone 1H, 15N and 13C nuclei in intrinsically disordered protein α-synuclein
Abstract Intrinsically disordered proteins (IDPs) are abundant in nature and characterization of their potential structural propensities remains a widely pursued but challenging task. Analysis of NMR secondary chemical shifts plays an important role in such studies, but the output of such analyses depends on the accuracy of reference random coil chemical shifts. Although uniform perdeuteration of IDPs can dramatically increase spectral resolution, a feature particularly...
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09-10-2012 01:48 AM
Intrinsically disordered proteins - PhysicsToday.org
Intrinsically disordered proteins - PhysicsToday.org
<img alt="" height="1" width="1" />
Intrinsically disordered proteins
PhysicsToday.org
Indeed, much of the community's understanding of protein function rests on our ability to deduce those structures by such methods as x-ray crystallography and nuclear magnetic resonance (NMR). The immense success and explanatory power of the ...
Read here
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08-01-2012 09:35 PM
Quantitative Analysisof Multisite Protein–LigandInteractions by NMR: Binding of Intrinsically Disordered p53 TransactivationSubdomains with the TAZ2 Domain of CBP
Quantitative Analysisof Multisite Protein–LigandInteractions by NMR: Binding of Intrinsically Disordered p53 TransactivationSubdomains with the TAZ2 Domain of CBP
Munehito Arai, Josephine C. Ferreon and Peter E. Wright
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja209936u/aop/images/medium/ja-2011-09936u_0012.gif
Journal of the American Chemical Society
DOI: 10.1021/ja209936u
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/ak4BxkITHl8
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02-16-2012 05:24 AM
In Situ Structural Characterization of a Recombinant Protein in Native Escherichia coli Membranes with Solid-State MAS NMR.
In Situ Structural Characterization of a Recombinant Protein in Native Escherichia coli Membranes with Solid-State MAS NMR.
In Situ Structural Characterization of a Recombinant Protein in Native Escherichia coli Membranes with Solid-State MAS NMR.
J Am Chem Soc. 2011 Jul 21;
Authors: Fu R, Wang X, Li C, Santiago-Miranda AN, Pielak GJ, Tian F
The feasibility of using solid state MAS NMR for in situ structural characterization of the LR11 (sorLA) transmembrane domain in native Escherichia coli (E. coli) membranes is presented. LR11 interacts with...
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07-23-2011 08:54 AM
Solid-state NMR sequential assignments of ?-synuclein.
Solid-state NMR sequential assignments of ?-synuclein.
Solid-state NMR sequential assignments of ?-synuclein.
Biomol NMR Assign. 2011 Jul 9;
Authors: Gath J, Habenstein B, Bousset L, Melki R, Meier BH, Böckmann A
Parkinson's disease is amongst the most frequent and most devastating neurodegenerative diseases. It is tightly associated with the assembly of proteins into high-molecular weight protein species, which propagate between neurons in the central nervous system. The principal protein involved in this process is ?-synuclein which is a...
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07-12-2011 06:23 PM
Solid-State NMR Reveals Structural and Dynamical Properties of a Membrane Protein
http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/2007/129/i21/abs/ja069028m.html
Solid-State NMR Reveals Structural and Dynamical Properties of a Membrane-Anchored Electron-Carrier Protein, Cytochrome b<sub>5</sub>
<aui auinm="Durr, U. H. N."> <aui auinm="Yamamoto, K."> <aui auinm="Im, S.-C."> <aui auinm="Waskell, L."> <aui auinm="Ramamoorthy, A."> <aug><aul></aul></aug></aui></aui></aui></aui></aui> <au>Ulrich H. N. Dürr,</au> <au>Kazutoshi Yamamoto,</au><au>Sang-Choul Im,</au><au>Lucy Waskell,and </au><au>Ayyalusamy Ramamoorthy*</au>
*ramamoor@umich.edu
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