Biophysical analysis of normal transthyretin: implications for fibril formation in senile systemic amyloidosis

Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis
C M ChungM T Walsh

Abstract

Transthyretin (TTR) is a plasma protein that transports thyroid hormone and retinol binding protein-vitamin A complex. Eighty-four variants of TTR have been identified and seventy-four are associated with familial amyloidotic polyneuropathy. Normal TTR is the major protein found in the fibrillar deposits in the heart at time of autopsy of individuals with senile systemic amyloidosis. The mechanism by which normally soluble TTR deposits as organ-damaging, insoluble, pathological fibrils late in life is unknown. Understanding the mechanism of fibrillogenesis of normal TTR is critical to the design of clinical treatments aimed at retardation, prevention, or reversal of fibril deposition. We have employed a biophysical approach to explore the hypothesis that an instability in a particular secondary or tertiary structure plays a role in the ability of normal TTR to form fibrils at physiological pH. Using far UV circular dichroic (CD) spectroscopy as a function of temperature we have identified simultaneous, cooperative, reversible structural changes in the beta-sheet and alpha-helical regions. The flexible short, surface-located loops undergo an irreversible conformational change at a lower temperature. Spectra before and after heat...Continue Reading

References

Sep 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H TowbinJ Gordon
Jan 1, 1978·Methods in Enzymology·K S Krishinan, J F Brandts
Jun 1, 1991·Journal of Electron Microscopy Technique·K Segawa, R Takiguchi
Sep 16, 1991·Biochemical and Biophysical Research Communications·L K SteinraufM D Benson
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P WestermarkG G Cornwell
Jul 1, 1990·Archives of Internal Medicine·R G Hutchinson
Jan 1, 1988·Advances in Protein Chemistry·P L Privalov, S J Gill
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·B E SchonerR G Schoner
Jul 21, 1972·Biochimica Et Biophysica Acta·A M GottoD S Goodman
Sep 1, 1969·Proceedings of the Society for Experimental Biology and Medicine·L BonarM M Skinner
Jun 1, 1967·The Journal of Cell Biology·T Shirahama, A S Cohen
Oct 1, 1983·The American Journal of Medicine·G G CornwellP Pitkänen
Dec 24, 1996·Proceedings of the National Academy of Sciences of the United States of America·G J MiroyJ W Kelly
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·P T Lansbury
Feb 1, 1963·The Journal of Clinical Investigation·S H INGBAR

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Citations

Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Simon E KolstoeMark B Pepys
Aug 3, 2007·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Anders Karlsson, A Elisabeth Sauer-Eriksson
Oct 1, 1990·Scandinavian Journal of Immunology·M J SaraivaM A Gawinowicz
Jul 30, 2008·Journal of Molecular Biology·Satheesh K PalaninathanJames C Sacchettini
May 23, 2003·Protein Science : a Publication of the Protein Society·Mingfeng YangShuanghong Huo
Apr 12, 2005·Biophysical Journal·Mingfeng YangShuanghong Huo
Jan 6, 2005·The American Journal of Pathology·Vickery Trinkaus-RandallMartha Skinner
Dec 19, 2012·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Zarina GioevaChristoph Röcken
Feb 24, 2007·Protein Expression and Purification·Jonathan S KingsburyLawreen H Connors
Jul 15, 2017·Acta Cardiologica·Hassan AlkhawamTimothy J Vittorio
May 17, 2017·Biophysics Reviews·Marja Steenman, Gilles Lande
Oct 16, 2015·The Journal of Biological Chemistry·Lorena SaelicesDavid S Eisenberg

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