Structural basis of Cu, Zn-superoxide dismutase amyloid fibril formation involves interaction of multiple peptide core regions

Journal of Biochemistry
Masataka IdaYasushi Kawata

Abstract

Cu, Zn-superoxide dismutase (SOD1), an enzyme implicated in the progression of familial amyotrophic lateral sclerosis (fALS), forms amyloid fibrils under certain experimental conditions. As part of our efforts to understand ALS pathogenesis, in this study we found that reduction of the intramolecular disulfide bond destabilized the tertiary structure of metal free wild-type SOD1 and greatly enhanced fibril formation in vitro. We also identified fibril core peptides that are resistant to protease digestion by using mass spectroscopy and Edman degradation analyses. Three regions dispersed throughout the sequence were detected as fibril core sequences of SOD1. Interestingly, by using three synthetic peptides that correspond to these identified regions, we determined that each region was capable of fibril formation, either alone or in a mixture containing multiple peptides. It was also revealed that by reducing the disulfide bond and causing a decrease in the structural stability, the amyloid fibril formation of a familial mutant SOD1 G93A was accelerated even under physiological conditions. These results demonstrate that by destabilizing the structure of SOD1 by removing metal ions and breaking the intramolecular disulfide bridge,...Continue Reading

References

Nov 20, 1978·Biochimica Et Biophysica Acta·R G Briggs, J A Fee
Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J D CrapoL Y Chang
Jan 1, 1994·Methods in Enzymology·F Sakiyama, T Masaki
Jul 19, 2000·Biochimica Et Biophysica Acta·L C Serpell
Apr 12, 2002·The Journal of Biological Chemistry·Dong-Pyo HongYuji Goto
Nov 5, 2002·Nature Reviews. Molecular Cell Biology·Carolyn S Sevier, Chris A Kaiser
Nov 30, 2002·The Journal of Biological Chemistry·Ashutosh Tiwari, Lawrence J Hayward
Dec 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mikael J LindbergMikael Oliveberg
Feb 28, 2003·Neurochemistry International·Barkur S Shastry
Oct 1, 2003·Biochemistry·Atta AhmadAnthony L Fink
Dec 20, 2003·Nature·Christopher M Dobson
Dec 20, 2003·Nature·Dennis J Selkoe
Dec 25, 2003·Journal of the American Society of Nephrology : JASN·Suguru YamamotoHironobu Naiki
May 4, 2004·BMC Bioinformatics·Shandar AhmadAkinori Sarai
May 12, 2004·Biochimica Et Biophysica Acta·Vladimir N Uversky, Anthony L Fink
Jun 26, 2004·Annual Review of Neuroscience·Lucie I BruijnDon W Cleveland
Jun 10, 2005·Nature·Rebecca NelsonDavid Eisenberg
Jun 15, 2005·Annual Review of Biochemistry·Joan Selverstone ValentineSoshanna Zittin Potter
Nov 18, 2005·The Journal of Biological Chemistry·Lucia BanciElena Gaggelli
Dec 7, 2005·Brain : a Journal of Neurology·P Andreas JonssonStefan L Marklund
Jul 4, 2006·Biochimica Et Biophysica Acta·Rishi Rakhit, Avijit Chakrabartty
Sep 1, 2006·The Journal of Biological Chemistry·Manuela BassoValentina Bonetto
Oct 31, 2006·Journal of Molecular Biology·Andreas HörnbergMikael Oliveberg
May 9, 2007·Nature Medicine·Rishi RakhitAvijit Chakrabartty
Aug 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Per ZetterströmStefan L Marklund
Dec 25, 2007·Journal of Molecular Biology·Kaori YamamotoYuji Goto
Feb 29, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dick JaarsmaCasper C Hoogenraad

❮ Previous
Next ❯

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.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.