Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism

被引：0
|
作者：
Ashwani K Thakur
Murali Jayaraman
Rakesh Mishra
Monika Thakur
Veronique M Chellgren
In-Ja L Byeon
Dalaver H Anjum
Ravindra Kodali
Trevor P Creamer
James F Conway
Angela M Gronenborn
Ronald Wetzel
机构：
[1] Department of Structural Biology,Department of Molecular and Cellular Biochemistry
[2] Pittsburgh Institute for Neurodegenerative Diseases,undefined
[3] University of Pittsburgh School of Medicine,undefined
[4] University of Kentucky,undefined
来源：
Nature Structural & Molecular Biology | 2009年 / 16卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The huntingtin protein (HTT) contains a polyQ tract preceded by an N-terminal flanking sequence (HTTNT) that contributes to HTT aggregation. Now the role of HTTNT in aggregation is explored in vitro, revealing a complex, multistep pathway initiated when polyQ disrupts HTTNT structure, enhancing the latter's assembly into prefibrillar aggregates. Within these intermediates, subsequent interactions of the polyQ moieties drive further assembly into compact amyloid aggregates.
引用
收藏
页码：380 / 389
页数：9
相关论文
共 50 条
  • [1] Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism
    Thakur, Ashwani K.
    Jayaraman, Murali
    Mishra, Rakesh
    Thakur, Monika
    Chellgren, Veronique M.
    Byeon, In-Ja L.
    Anjum, Dalaver H.
    Kodali, Ravindra
    Creamer, Trevor P.
    Conway, James F.
    Gronenborn, Angela M.
    Wetzel, Ronald
    NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2009, 16 (04) : 380 - 389
  • [2] Discovery of Arginine Ethyl Ester as Polyglutamine Aggregation Inhibitor: Conformational Transitioning of Huntingtin N-Terminus Augments Aggregation Suppression
    Singh, Virender
    Patel, Kinjal A.
    Sharma, Raj Kumar
    Patil, Pratik R.
    Joshi, Abhayraj S.
    Parihar, Rashmi
    Athilingam, Thamarailingam
    Sinha, Neeraj
    Ganesh, Subramaniam
    Sinha, Pradip
    Roy, Ipsita
    Thakur, Ashwani Kumar
    ACS CHEMICAL NEUROSCIENCE, 2019, 10 (09): : 3969 - 3985
  • [3] Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation
    Crick, Scott L.
    Ruff, Kiersten M.
    Garai, Kanchan
    Frieden, Carl
    Pappu, Rohit V.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (50) : 20075 - 20080
  • [4] Modulation of Polyglutamine Conformations and Dimer Formation by the N-Terminus of Huntingtin
    Williamson, Tim E.
    Vitalis, Andreas
    Crick, Scott L.
    Pappu, Rohit V.
    JOURNAL OF MOLECULAR BIOLOGY, 2010, 396 (05) : 1295 - 1309
  • [5] Huntingtin affinity for partners is not changed by polyglutamine length: aggregation itself triggers aberrant interactions
    Davranche, Aurelien
    Aviolat, Hubert
    Zeder-Lutz, Gabrielle
    Busso, Didier
    Altschuh, Daniele
    Trottier, Yvon
    Klein, Fabrice A. C.
    HUMAN MOLECULAR GENETICS, 2011, 20 (14) : 2795 - 2806
  • [6] Structure and Dynamics of the Huntingtin Exon-1 N-Terminus: A Solution NMR Perspective
    Baias, Maria
    Smith, Pieter E. S.
    Shen, Koning
    Joachimiak, Lukasz A.
    Zerko, Szymon
    Kozminski, Wiktor
    Frydman, Judith
    Frydman, Lucio
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2017, 139 (03) : 1168 - 1176
  • [7] Membrane Interactions Accelerate the Self-Aggregation of Huntingtin Exon 1 Fragments in a Polyglutamine Length-Dependent Manner
    Marquette, Arnaud
    Aisenbrey, Christopher
    Bechinger, Burkhard
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (13)
  • [8] Polyglutamine Length Dependent Structural Properties and Phase Behavior of Huntingtin Exon 1
    Ruff, Kiersten M.
    Warner, John B.
    Posey, Ammon E.
    Tan, Piau Siong
    Lemke, Edward A.
    Pappu, Rohit V.
    Lashuel, Hilal A.
    BIOPHYSICAL JOURNAL, 2017, 112 (03) : 511A - 511A
  • [9] The folding equilibrium of huntingtin exon 1 monomer depends on its polyglutamine tract
    Bravo-Arredondo, Jose M.
    Kegulian, Natalie C.
    Schmidt, Thomas
    Pandey, Nitin K.
    Situ, Alan J.
    Ulmer, Tobias S.
    Langen, Ralf
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 293 (51) : 19613 - 19623
  • [10] Polyglutamine Induced Misfolding of Huntingtin Exon1 is Modulated by the Flanking Sequences
    Lakhani, Vinal V.
    Ding, Feng
    Dokholyan, Nikolay V.
    PLOS COMPUTATIONAL BIOLOGY, 2010, 6 (04)
12345