α-Synuclein mutations cluster around a putative protein loop

被引：35

作者：

Kara, Eleanna ^{[1
]}

Lewis, Patrick A. ^{[1
,2
]}

Ling, Helen ^{[1
]}

Proukakis, Christos ^{[3
]}

Houlden, Henry ^{[1
]}

Hardy, John ^{[1
]}

机构：

[1] UCL Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London WC1N 3BG, England

[2] Univ Reading, Sch Pharm, Reading RG6 6AP, Berks, England

[3] Inst Neurol, Dept Clin Neurosci, London NW3 2PF, England

来源：

NEUROSCIENCE LETTERS | 2013年 / 546卷

基金：

英国惠康基金;

关键词：

alpha-Synuclein; SNCA; Genetics; Parkinson's disease; CHAPERONE-MEDIATED AUTOPHAGY; PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASE; BETA-SYNUCLEIN; LEWY BODIES; TRIPLICATION; NEURONS; BINDING; LOCUS; FORMS;

D O I：

10.1016/j.neulet.2013.04.058

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

With the recent identification of two new pathogenic mutations in a-synuclein, we map the five known pathogenic mutations onto the best available models of the protein structure. We show that four of the five mutations map to a potential fold in the protein with the exception being the MOP mutation in which the substitution would be expected to have a profound effect on protein structure. We discuss this localisation in terms of the proposed mechanisms for mutation pathogenicity. (C) 2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.

引用

页码：67 / 70

页数：4

共 43 条

[1] Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease [J].

Appel-Cresswell, Silke ;

Vilarino-Guell, Carles ;

Encarnacion, Mary ;

Sherman, Holly ;

Yu, Irene ;

Shah, Brinda ;

Weir, David ;

Thompson, Christina ;

Szu-Tu, Chelsea ;

Trinh, Joanne ;

Aasly, Jan O. ;

Rajput, Alex ;

Rajput, Ali H. ;

Stoessl, A. Jon ;

Farrer, Matthew J. .

MOVEMENT DISORDERS, 2013, 28 (06) :811-813

[2] α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation [J].

Bartels, Tim ;

Choi, Joanna G. ;

Selkoe, Dennis J. .

NATURE, 2011, 477 (7362) :107-U123

[3] Site-specific interactions of Cu(II) with α and β-synuclein:: Bridging the molecular gap between metal binding and aggregation [J].

Binolfi, Andres ;

Lamberto, Gonzalo R. ;

Duran, Rosario ;

Quintanar, Liliana ;

Bertoncini, Carlos W. ;

Souza, Jose M. ;

Cervenansky, Carlos ;

Zweckstetter, Markus ;

Griesinger, Christian ;

Fernandez, Clauclio O. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (35) :11801-11812

[4] Bacterial in-cell NMR of human α-synuclein: a disordered monomer by nature? [J].

Binolfi, Andres ;

Theillet, Francois-Xavier ;

Selenko, Philipp .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2012, 40 :950-U292

[5] Staging of brain pathology related to sporadic Parkinson's disease [J].

Braak, H ;

Del Tredici, K ;

Rüb, U ;

de Vos, RAI ;

Steur, ENHJ ;

Braak, E .

NEUROBIOLOGY OF AGING, 2003, 24 (02) :197-211

[6] α-synuclein locus duplication as a cause of familial Parkinson's disease [J].

Chartier-Harlin, MC ;

Kachergus, J ;

Roumier, C ;

Mouroux, V ;

Douay, X ;

Lincoln, S ;

Levecque, C ;

Larvor, L ;

Andrieux, J ;

Hulihan, M ;

Waucquier, N ;

Defebvre, L ;

Amouyel, P ;

Farrer, M ;

Destée, A .

LANCET, 2004, 364 (9440) :1167-1169

[7] Direct Observation of the Interconversion of Normal and Toxic Forms of α-Synuclein [J].

Cremades, Nunilo ;

Cohen, Samuel I. A. ;

Deas, Emma ;

Abramov, Andrey Y. ;

Chen, Allen Y. ;

Orte, Angel ;

Sandal, Massimo ;

Clarke, Richard W. ;

Dunne, Paul ;

Aprile, Francesco A. ;

Bertoncini, Carlos W. ;

Wood, Nicholas W. ;

Knowles, Tuomas P. J. ;

Dobson, Christopher M. ;

Klenerman, David .

CELL, 2012, 149 (05) :1048-1059

[8] NMR determination of pKa values in α-synuclein [J].

Croke, Robyn L. ;

Patil, Sharadrao M. ;

Quevreaux, Jason ;

Kendall, Debra A. ;

Alexandrescu, Andrei T. .

PROTEIN SCIENCE, 2011, 20 (02) :256-269

[9] Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy [J].

Cuervo, AM ;

Stefanis, L ;

Fredenburg, R ;

Lansbury, PT ;

Sulzer, D .

SCIENCE, 2004, 305 (5688) :1292-1295

[10] 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

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