Molecular basis for the Cu2+ binding-induced destabilization of beta2-microglobulin revealed by molecular dynamics simulation

Biophysical Journal
Nan-Jie DengPiotr Cieplak

Abstract

According to experimental data, binding of the Cu(2+) ions destabilizes the native state of beta2-microglobulin (beta2m). The partial unfolding of the protein was generally considered an early step toward fibril formation in dialysis-related amyloidosis. Recent NMR studies have suggested that the destabilization of the protein might be achieved through increased flexibility upon Cu(2+) binding. However, the molecular mechanism of destabilization due to Cu(2+), its role in amyloid formation, and the relative contributions of different potential copper-binding sites remain unclear. To elucidate the effect of ion ligation at atomic detail, a series of molecular dynamics simulations were carried out on apo- and Cu(2+)-beta2m systems in explicit aqueous solutions, with varying numbers of bound ions. Simulations at elevated temperatures (360 K) provide detailed pictures for the process of Cu(2+)-binding-induced destabilization of the native structure at the nanosecond timescale, which are in agreement with experiments. Conformational transitions toward partially unfolded states were observed in protein solutions containing bound copper ions at His-31 and His-51, which is marked by an increase in the protein vibrational entropy, with ...Continue Reading

References

Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M M YamashitaD Eisenberg
Dec 1, 1987·Biophysical Journal·M KarplusB M Pettitt
Jan 1, 1996·Nephron·J Floege, G Ehlerding
Jan 1, 1996·Annual Review of Physical Chemistry·K T DayieJ F Lefèvre
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
Jun 4, 1999·Biophysical Journal·R D LinsJ A McCammon
Mar 30, 2001·The Journal of Biological Chemistry·M L KramerH Kretzschmar
May 24, 2001·Journal of Molecular Biology·C J MorganA D Miranker
Jul 21, 2001·Biophysical Journal·S Y Noskov, C Lim
Aug 21, 2002·Biochemistry·Catherine M EakinAndrew D Miranker
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus
Sep 1, 2005·Journal of Chemical Theory and Computation·Chia-En ChangMichael K Gilson

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Citations

Feb 24, 2011·Journal of the American Chemical Society·Sudhakar ParthasarathyYoshitaka Ishii
Jul 28, 2010·The Journal of Biological Chemistry·Leonardo de C PalmieriDebora Foguel
Jun 25, 2008·Annual Review of Biophysics·Todor Dudev, Carmay Lim
Jul 21, 2007·Reproduction : the Official Journal of the Society for the Study of Fertility·B A QuinnK J Betteridge
Feb 3, 2009·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Xiaolong XuJiehua Li
Jan 5, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Dengke ShenQingde Su
Nov 18, 2011·Molecular Biology International·Isidoros IakovidisStylianos M Piperakis
Nov 17, 2012·Journal of Molecular Biology·Atsushi MukaiyamaKunihiro Kuwajima
Aug 7, 2009·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Niels H H Heegaard
Oct 21, 2017·Molecular BioSystems·Cedrix J Dongmo FoumthuimFederico Fogolari
May 21, 2011·The FEBS Journal·Timo Eichner, Sheena E Radford
May 23, 2012·Physical Chemistry Chemical Physics : PCCP·Samuel Genheden, Ulf Ryde
Jan 1, 2007·Prion·Guanghong WeiPhilippe Derreumaux
Nov 3, 2020·Frontiers in Molecular Biosciences·Rui J S Loureiro, Patrícia F N Faísca
Sep 10, 2008·The American Journal of Clinical Nutrition·Vishal Desai, Stephen G Kaler
Nov 10, 2020·Journal of the American Chemical Society·Marta BonaccorsiGuido Pintacuda

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