Broken helix in vesicle and micelle-bound α-synuclein:: Insights from site-directed spin labeling-EPR experiments and MD simulations

被引：65

作者：

Bortolus, Marco ^{[1
]}

Tombolato, Fabio ^{[1
]}

Tessari, Isabella ^{[2
]}

Bisaglia, Marco ^{[2
]}

Mammi, Stefano ^{[1
]}

Bubacco, Luigi ^{[2
]}

Ferrarini, Alberta ^{[1
]}

Maniero, Anna Lisa ^{[1
]}

机构：

[1] Univ Padua, Dipartimento Sci Chim, I-35131 Padua, Italy

[2] Univ Padua, Dipartimento Biol, I-35121 Padua, Italy

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2008年 / 130卷 / 21期

关键词：

D O I：

10.1021/ja8010429

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The region 35-43 of human alpha-Synuclein bound to small unilamellar lipid vesicles and to sodium dodecyl sulfate micelles has been investigated by site-directed spin labeling and electron paramagnetic resonance spectroscopy. The distance distributions obtained from spectral fitting have been analyzed on the basis of the allowed rotamers of the spin-label side-chain. Very similar results have been obtained in the two environments: an unbroken helical structure of the investigated region can be ruled out. The distance distributions are rather compatible with the presence of conformational disorder, in agreement with previous findings for micelle-bound a-Synuclein. The propensity for helix breaking is confirmed by molecular dynamics simulations.

引用

页码：6690 / +

页数：3

共 16 条

[1] De novo high-resolution protein structure determination from sparse spin-labeling EPR data [J].

Alexander, Nathan ;

Bortolus, Marco ;

Al-Mestarihi, Ahmad ;

Mchaourab, Hassane ;

Meilerl, Jens .

STRUCTURE, 2008, 16 (02) :181-195

[2] Estimation of inter-residue distances in spin labeled proteins at physiological temperatures: Experimental strategies and practical limitations [J].

Altenbach, C ;

Oh, KJ ;

Trabanino, RJ ;

Hideg, K ;

Hubbell, WL .

BIOCHEMISTRY, 2001, 40 (51) :15471-15482

[3] A topological model of the interaction between α-synuclein and sodium dodecyl sulfate micelles [J].

Bisaglia, M ;

Tessari, I ;

Pinato, L ;

Bellanda, M ;

Giraudo, S ;

Fasano, M ;

Bergantino, E ;

Bubacco, L ;

Mammi, S .

BIOCHEMISTRY, 2005, 44 (01) :329-339

[4] Inter-helix distances in lysophospholipid micelle-bound α-synuclein from pulsed ESR measurements [J].

Borbat, Peter ;

Ramlall, Trudy F. ;

Freed, Jack H. ;

Eliezer, David .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (31) :10004-10005

[5] A structural and functional role for 11-mer repeats in α-synuclein and other exchangeable lipid binding proteins [J].

Bussell, R ;

Eliezer, D .

JOURNAL OF MOLECULAR BIOLOGY, 2003, 329 (04) :763-778

[6] A broken α-helix in folded α-synuclein [J].

Chandra, S ;

Chen, XC ;

Rizo, J ;

Jahn, R ;

Südhof, TC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (17) :15313-15318

[7] Stabilization of α-synuclein secondary structure upon binding to synthetic membranes [J].

Davidson, WS ;

Jonas, A ;

Clayton, DF ;

George, JM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (16) :9443-9449

[8] Conformational properties of α-synuclein in its free and lipid-associated states [J].

Eliezer, D ;

Kutluay, E ;

Bussell, R ;

Browne, G .

JOURNAL OF MOLECULAR BIOLOGY, 2001, 307 (04) :1061-1073

[9] THE PRECURSOR PROTEIN OF NON-A-BETA COMPONENT OF ALZHEIMERS-DISEASE AMYLOID IS A PRESYNAPTIC PROTEIN OF THE CENTRAL-NERVOUS-SYSTEM [J].

IWAI, A ;

MASLIAH, E ;

YOSHIMOTO, M ;

GE, NF ;

FLANAGAN, L ;

DESILVA, HAR ;

KITTEL, A ;

SAITOH, T .

NEURON, 1995, 14 (02) :467-475

[10] Structure of membrane-bound α-synuclein studied by site-directed spin labeling [J].

Jao, CC ;

Der-Sarkissian, A ;

Chen, J ;

Langen, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (22) :8331-8336

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