Amyloidosis has been found to be responsible for a growing number of misfolding disorders. Although several amyloid diseases are fatal and most are very severe, to date no effective treatment to any of the amyloid related diseases is available. In order to characterize the structural aspects of protein aggregation, the three main species present during amyloid aggregation have to be studied: the starting native fold, the oligomers and the mature amyloid fibrils. Beta-2 microglobulin (b2m) is an amylodogenic protein responsible for Dialysis Related Amyloidosis a disorder resulting in severe movement impairment. Aiming to understand the structural determinants of b2m aggregation propensity, we have characterised the role of the DE loop in the monomeric b2m. Mutations in such loop revealed that modifying the geometry of the DE loop has global effects on b2m: such mutations affect b2m folding, fold stability, structure, amyloidogenic propensity and dynamics under native and denaturating conditions. Such effects have been studied by several techniques such as X-ray crystallography, circular dichroism, intrinsic fluorescence, mass spectrometry and infrared spectroscopy. In order to shed light on the structural details of b2m aggregation, a strategy to form artificial oligomers amenable for crystallographic studies have been designed and it will be shown together with the structures of two artificial oligomers and their propensity to form amyloid fibrils. Finally ssNMR experiments on double and triple labelled samples of crystalline and fibrillar b2m will be presented. In particular spectra of crystalline and aggregated b2m reveal that the most of b2m is structured in amyloid fibrils

Ricagno, S., Colombo, M., Grandori, R., Doglia, S., Pintacuda, G., Bellotti, V., et al. (2012). Studying amyloidogenic beta-2 microglobulin: the monomer, the oligomers and the fibrils. In The 26th Annual Symposium of The Protein Society: Abstracts (pp.186-187). Cambridge University Press [10.1002/pro.2113].

Studying amyloidogenic beta-2 microglobulin: the monomer, the oligomers and the fibrils

GRANDORI, RITA;DOGLIA, SILVIA MARIA;
2012

Abstract

Amyloidosis has been found to be responsible for a growing number of misfolding disorders. Although several amyloid diseases are fatal and most are very severe, to date no effective treatment to any of the amyloid related diseases is available. In order to characterize the structural aspects of protein aggregation, the three main species present during amyloid aggregation have to be studied: the starting native fold, the oligomers and the mature amyloid fibrils. Beta-2 microglobulin (b2m) is an amylodogenic protein responsible for Dialysis Related Amyloidosis a disorder resulting in severe movement impairment. Aiming to understand the structural determinants of b2m aggregation propensity, we have characterised the role of the DE loop in the monomeric b2m. Mutations in such loop revealed that modifying the geometry of the DE loop has global effects on b2m: such mutations affect b2m folding, fold stability, structure, amyloidogenic propensity and dynamics under native and denaturating conditions. Such effects have been studied by several techniques such as X-ray crystallography, circular dichroism, intrinsic fluorescence, mass spectrometry and infrared spectroscopy. In order to shed light on the structural details of b2m aggregation, a strategy to form artificial oligomers amenable for crystallographic studies have been designed and it will be shown together with the structures of two artificial oligomers and their propensity to form amyloid fibrils. Finally ssNMR experiments on double and triple labelled samples of crystalline and fibrillar b2m will be presented. In particular spectra of crystalline and aggregated b2m reveal that the most of b2m is structured in amyloid fibrils
paper
Amyloid aggregation, beta-2 microglobulin, oligomers, fibrils, Dialysis Related Amyloidosis
English
The 26th Annual Symposium of The Protein Society
2012
Ricagno, S; Colombo, M; Grandori, R; Doglia, S; Pintacuda, G; Bellotti, V; Bolognesi, M
Bowie, J; Regan, L; Raleigh, D; Fetrow, J; Baum, J; Palmer III, AG; Matthews, B
The 26th Annual Symposium of The Protein Society: Abstracts
2012
21
S1
186
187
none
Ricagno, S., Colombo, M., Grandori, R., Doglia, S., Pintacuda, G., Bellotti, V., et al. (2012). Studying amyloidogenic beta-2 microglobulin: the monomer, the oligomers and the fibrils. In The 26th Annual Symposium of The Protein Society: Abstracts (pp.186-187). Cambridge University Press [10.1002/pro.2113].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/36671
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