Literature DB >> 26695014

Phase transitions and structure analysis in wild-type, A30P, E46K, and A53T mutants of α-synuclein.

Mark A Healey1, Michael T Woodside1,2, Jack A Tuszynski3,4.   

Abstract

α-Synuclein has been implicated in the development of neural plaques in Parkinson's Disease and Lewy-Body Dementia. This paper reports on the structural phase change behavior exhibited over a relevant range of temperatures in canonical protein Monte Carlo simulations for wild-type α-synuclein and three of its familial variants. We performed and analyzed these simulations to determine residue occupancy variations above and below this phase transition. From this analysis, we found regions above the phase transition temperature that consistently exhibited increased propensity for formation of long-chain beta-sheets, suggesting a possible role in α-synuclein aggregation.

Entities:  

Keywords:  Intrinsically disordered protein; Monte Carlo simulations; Mutations; Parkinson’s disease; Phase transitions; α-Synuclein

Mesh：

Substances：

Year:  2015        PMID： 26695014     DOI： 10.1007/s00249-015-1103-0

Source DB:  PubMed          Journal:  Eur Biophys J        ISSN： 0175-7571            Impact factor:   1.733


  45 in total

1.  Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation.

Authors:  L C Serpell; J Berriman; R Jakes; M Goedert; R A Crowther
Journal:  Proc Natl Acad Sci U S A       Date:  2000-04-25       Impact factor: 11.205

2.  Self-consistent 3J coupling analysis for the joint calibration of Karplus coefficients and evaluation of torsion angles.

Authors:  J M Schmidt; M Blümel; F Löhr; H Rüterjans
Journal:  J Biomol NMR       Date:  1999-05       Impact factor: 2.835

3.  The impact of the E46K mutation on the properties of alpha-synuclein in its monomeric and oligomeric states.

Authors:  Ross A Fredenburg; Carla Rospigliosi; Robin K Meray; Jeffrey C Kessler; Hilal A Lashuel; David Eliezer; Peter T Lansbury
Journal:  Biochemistry       Date:  2007-05-26       Impact factor: 3.162

4.  Distinct phases of free α-synuclein--a Monte Carlo study.

Authors:  Sigurður Aegir Jónsson; Sandipan Mohanty; Anders Irbäck
Journal:  Proteins       Date:  2012-06-12

5.  Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation.

Authors:  L Narhi; S J Wood; S Steavenson; Y Jiang; G M Wu; D Anafi; S A Kaufman; F Martin; K Sitney; P Denis; J C Louis; J Wypych; A L Biere; M Citron
Journal:  J Biol Chem       Date:  1999-04-02       Impact factor: 5.157

6.  Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein.

Authors:  Woong Choi; Shahin Zibaee; Ross Jakes; Louise C Serpell; Bazbek Davletov; R Anthony Crowther; Michel Goedert
Journal:  FEBS Lett       Date:  2004-10-22       Impact factor: 4.124

7.  Investigation of alpha-synuclein fibril structure by site-directed spin labeling.

Authors:  Min Chen; Martin Margittai; Jeannie Chen; Ralf Langen
Journal:  J Biol Chem       Date:  2007-06-15       Impact factor: 5.157

8.  Alteration of the alpha-synuclein folding landscape by a mutation related to Parkinson's disease.

Authors:  Allan Chris M Ferreon; Crystal R Moran; Josephine C Ferreon; Ashok A Deniz
Journal:  Angew Chem Int Ed Engl       Date:  2010-05-03       Impact factor: 15.336

9.  Structures and free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins with dynamics.

Authors:  Olivia Wise-Scira; Ahmet Kemal Aloglu; Aquila Dunn; Isin Tuna Sakallioglu; Orkid Coskuner
Journal:  ACS Chem Neurosci       Date:  2013-01-30       Impact factor: 4.418

Review 10.  The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease.

Authors:  D F Clayton; J M George
Journal:  Trends Neurosci       Date:  1998-06       Impact factor: 13.837
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  4 in total

1.  Probing the Basis of α-Synuclein Aggregation by Comparing Simulations to Single-Molecule Experiments.

Authors:  Cassandra D M Churchill; Mark A Healey; Jordane Preto; Jack A Tuszynski; Michael T Woodside
Journal:  Biophys J       Date:  2019-08-16       Impact factor: 4.033

Review 2.  Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.

Authors:  Phuong H Nguyen; Ayyalusamy Ramamoorthy; Bikash R Sahoo; Jie Zheng; Peter Faller; John E Straub; Laura Dominguez; Joan-Emma Shea; Nikolay V Dokholyan; Alfonso De Simone; Buyong Ma; Ruth Nussinov; Saeed Najafi; Son Tung Ngo; Antoine Loquet; Mara Chiricotto; Pritam Ganguly; James McCarty; Mai Suan Li; Carol Hall; Yiming Wang; Yifat Miller; Simone Melchionna; Birgit Habenstein; Stepan Timr; Jiaxing Chen; Brianna Hnath; Birgit Strodel; Rakez Kayed; Sylvain Lesné; Guanghong Wei; Fabio Sterpone; Andrew J Doig; Philippe Derreumaux
Journal:  Chem Rev       Date:  2021-02-05       Impact factor: 60.622

3.  The structural heterogeneity of α-synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds.

Authors:  Jiaxing Chen; Sofia Zaer; Paz Drori; Joanna Zamel; Khalil Joron; Nir Kalisman; Eitan Lerner; Nikolay V Dokholyan
Journal:  Structure       Date:  2021-05-19       Impact factor: 5.871

4.  Neuroprotective Effects of Betulin in Pharmacological and Transgenic Caenorhabditis elegans Models of Parkinson's Disease.

Authors:  Chia-Wen Tsai; Rong-Tzong Tsai; Shih-Ping Liu; Chang-Shi Chen; Min-Chen Tsai; Shao-Hsuan Chien; Huey-Shan Hung; Shinn-Zong Lin; Woei-Cherng Shyu; Ru-Huei Fu
Journal:  Cell Transplant       Date:  2017-12       Impact factor: 4.064
  4 in total

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