Insights into amyotrophic lateral sclerosis linked Pro525Arg mutation in the fused in sarcoma protein through in silico analysis and molecular dynamics simulation.

Journal of Biomolecular Structure & Dynamics
Sompriya ChatterjeeJin Yong Lee

Abstract

A novel heterozygous mutation, Pro525Arg (P525R) in the Fused in Sarcoma (FUS) protein is predominant in young adult females with familial amyotrophic lateral sclerosis (fALS). Investigation of the biophysical characteristics of this mutation through analysis of protein conformation could provide insights into the pathogenic mechanism of amyotrophic lateral sclerosis (ALS). Here, several computational prediction tools were applied to investigate the effect of P525R on the stability, flexibility, and function of FUS. Conservation and biochemical analyses showed that P525 is highly conserved; the mutation of proline to arginine at position 525 in FUS results in a notable increase in molecular weight, number of hydrogen bonds, and loss of hydrophobicity. By performing electrostatic potential, intra-protein interaction, and binding affinity analyses, we found increased electrostatic potential charge in the mutant protein and fewer hydrophobic interactions than the wild-type structure. Binding affinity of the FUS nuclear localization signal (NLS) mutant for transportin (Trn1) was also decreased compared to wild-type. Our molecular dynamics (MD) simulation results highlighted the exchange between hydrophobic and hydrophilic residues ...Continue Reading

References

Aug 7, 1990·Biochemistry·K A Dill
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
May 31, 2002·Acta Crystallographica. Section D, Biological Crystallography·Helen M BermanChristine Zardecki
Jan 1, 1959·Advances in Protein Chemistry·W KAUZMANN
Feb 12, 2004·Journal of Molecular Recognition : JMR·Hans Rudolf BosshardIlian Jelesarov
Jun 28, 2005·Nucleic Acids Research·Emidio CapriottiRita Casadio
Jun 23, 2007·Nucleic Acids Research·K G TinaN Srinivasan
Jan 21, 2009·Cell Research·Jian RenXuebiao Yao
Feb 25, 2009·Bioinformation·Susan CostantiniAngelo M Facchiano
Dec 19, 2009·Neurobiology of Aging·Carsten DrepperMichael Sendtner
Jul 8, 2010·The EMBO Journal·Dorothee DormannChristian Haass
Feb 8, 2011·Lancet·Matthew C KiernanMargaret C Zoing
Apr 29, 2011·Folia Histochemica Et Cytobiologica·Jacek Z Kubiak
Jun 28, 2011·Trends in Neurosciences·Dorothee Dormann, Christian Haass
Aug 19, 2011·Prion·Aaron D Gitler, James Shorter
Mar 8, 2012·PLoS Computational Biology·Deeptak VermaDennis R Livesay
Jun 20, 2012·Bioinformatics·Ian WalshFederico Fogolari
Feb 13, 2013·BMC Bioinformatics·Chi-Wei ChenYen-Wei Chu
Mar 19, 2013·Journal of Molecular Graphics & Modelling·Andre A S T Ribeiro, Ricardo B de Alencastro
May 1, 2013·The Journal of Cell Biology·Yun R LiAaron D Gitler
May 16, 2013·Acta Neuropathologica·Anna M BlokhuisR Jeroen Pasterkamp
Jun 1, 2013·Nucleic Acids Research·Yves DehouckDimitri Gilis
Jan 24, 2014·PLoS Computational Biology·Jaroslav BendlJiri Damborsky
Apr 18, 2014·Journal of Biomolecular Structure & Dynamics·Balu KamarajRituraj Purohit
Jun 12, 2014·Nature Communications·R Bryn FenwickXavier Salvatella
Apr 18, 2015·BMC Bioinformatics·Josef LaimerPeter Lackner
May 2, 2015·The Journal of Clinical Investigation·Owen M PetersRobert H Brown
Jan 13, 2016·Journal of Neurochemistry·Arun Kumar Somavarapu, Kasper P Kepp
Apr 2, 2016·Brain Research·Yulei Shang, Eric J Huang
May 21, 2016·Nucleic Acids Research·Damiano PiovesanSilvio C E Tosatto
Sep 8, 2016·Acta Neuropathologica Communications·Matthew NolanOlaf Ansorge
Nov 11, 2016·Nature·J Paul TaylorDon W Cleveland
Apr 30, 2017·Nucleic Acids Research·Víctor López-FerrandoJosep Ll Gelpí

❮ Previous
Next ❯

Citations

Nov 5, 2020·ACS Chemical Neuroscience·Sompriya ChatterjeeJin Yong Lee
Sep 14, 2021·The Journal of Physical Chemistry Letters·Abhinaw KumarD Thirumalai

❮ Previous
Next ❯

Methods Mentioned

BETA
protein folding

Software Mentioned

mCSM
SASA
DOG
PDB viewer
Amber Tools
PON
SIFT
PIC
DUET
Amino explorer

Related Concepts

Related Feeds

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.