Comparative Analysis of the Conformation, Aggregation, Interaction, and Fibril Morphologies of Human α-, β-, and γ-Synuclein Proteins

Biochemistry
Manish Kumar JainRajiv Bhat

Abstract

The human synuclein (syn) family is comprised of α-, β-, and γ-syn proteins. α-syn has the highest propensity for aggregation, and its aggregated forms accumulate in Lewy bodies (LB) and Lewy neurites, which are involved in Parkinson's disease (PD). β- and γ-syn are absent in LB, and their exact role is still enigmatic. β-syn does not form aggregates under physiological conditions (pH 7.4), while γ-syn is associated with neural and non-neural diseases like breast cancer. Because of their similar regional distribution in the brain, natively unfolded structure, and high degree of sequence homology, studying the effect of the environment on their conformation, interactions, fibrillation, and fibril morphologies has become important. Our studies show that high temperatures, low pH values, and high concentrations increase the rate of fibrillation of α- and γ-syn, while β-syn forms fibrils only at low pH. Fibril morphologies are strongly dependent on the immediate environment of the proteins. The high molar ratio of β-syn inhibits the fibrillation in α- and γ-syn. However, preformed seed fibrils of β- and γ-syn do not affect fibrillation of α-syn. Surface plasmon resonance data show that interactions between α- and β-syn, β- and γ-sy...Continue Reading

References

Dec 1, 1990·Journal of Neurochemistry·S NakajoY Nakamura
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·R L Baldwin
Sep 8, 1995·The Journal of Biological Chemistry·A N Akopian, J N Wood
May 23, 1994·FEBS Letters·R JakesM Goedert
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K UédaT Saitoh
Aug 28, 1997·Nature·M G SpillantiniM Goedert
Aug 28, 1997·Biochemical and Biophysical Research Communications·M HashimotoE Masliah
Apr 18, 1998·Neuroscience Letters·K WakabayashiH Takahashi
Sep 16, 1998·Human Genetics·C LavedanM H Polymeropoulos
Sep 29, 1998·Genome Research·C Lavedan
Feb 2, 1999·Experimental Cell Research·N N NinkinaV L Buchman
Feb 23, 1999·Methods in Molecular Biology·M R WilkinsD F Hochstrasser
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·M Goedert
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·J E GalvinJ Q Trojanowski
Jan 22, 2001·The Journal of Biological Chemistry·V N UverskyA L Fink
Feb 15, 2001·Archives of Neurology·J E GalvinJ Q Trojanowski
Feb 24, 2001·Annals of the New York Academy of Sciences·M G Spillantini, M Goedert
Feb 24, 2001·Annals of the New York Academy of Sciences·K A ConwayP T Lansbury
Feb 24, 2001·Protein Science : a Publication of the Protein Society·T D KimJ Kim
Feb 24, 2001·Cellular and Molecular Life Sciences : CMLS·C B Lücking, A Brice
Apr 5, 2001·Journal of Molecular Biology·D EliezerG Browne
Jul 4, 2001·Nature Reviews. Neuroscience·M Goedert
Nov 1, 2001·Brain Research. Molecular Brain Research·J E PaytonJ M George
Jan 25, 2002·Genome Biology·Julia M George

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