*Villar-Piqué et al., (2012) The effect of amyloidogenic
peptides on bacterial aging correlates with their intrinsic
aggregation propensity. J. Mol. Biol. (in press) - XRB Annual Meeting 2012
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Anna Villar-Piqué (IBB) - AMYLOIDOGENIC PEPTIDES PROMOTE BACTERIAL AGING*
1. AMYLOIDOGENIC PEPTIDES
PROMOTE BACTERIAL AGING*
Anna Villar-Piqué, Natalia S. de Groot, Raimon Sabaté,
Xavier Fernàndez-Busquets and Salvador Ventura
*Villar-Piqué et al., (2012) The effect of amyloidogenic
peptides on bacterial aging correlates with their intrinsic
aggregation propensity. J. Mol. Biol. (in press)
Jornada Científica XRB, 2012
2. SUMMARY
Aβ42 - GFP GFP as a reporter of aggregation
Aggregation in E. coli
Protein aggregation
(Inclusion bodies)
Cell aging Role of IBs during division
3. Amyloid-like protein aggregation
Hartl et al., 2009
de Groot et al., 2009
- Binding amyloid dyes (ThT/CR)
- High β-sheet content
- Visible fibrils (PK treatment)
Dasari et al., 2011
4. GFP as a reporter of intracellular protein aggregation
Aβ42 variants with different
aggregation propensities
Low aggregation propensity
GFP folded
High fluorescence
Wurth et al., 2002
5. E. coli cell division and distribution of IBs
Tyedmers et al., 2010
Lindner et al., 2007
Lindner et al., 2007
6. Aβ42wt-GFP
20 different variants of Aβ42
that differ in the aminoacid of
the 19th position
“Ladder” of 20 different
aggregation propensities
Aβ42F19D-GFP
Different fluorescence
(de Groot & Ventura, 2006)
7. In vivo kinetic competition between folding and aggregation
Aβ42wt-GFP
Aβ42F19D-GFP
8. Chemical denaturation with Gnd HCl
Intrinsic aggregation propensity correlates with
conformational stability
14. Disaggregating: ClpB
Co-expression with molecular chaperones
Folding: DnaK & GroELS
(de Marco et el., 2007)
Control Disaggregating Both Folding
Aβ42wt-GFP
Aβ42F19D-GFP
16. Conclusions
Aβ42 sequence regulates IBs aggregation rate.
IBs aggregation rate determines their structural properties.
Aβ42 IBs cause a loss in the reproductive ability.
Cell aging depends on the aggregation propensity of Aβ42.
Chaperones alleviate aging effects.
17. Acknowledgements
Protein Folding and Design Group
-Salvador Ventura, Prof.
-Hugo Fraga, PhD
-Susanna Navarro, PhD
-Alba Espargaró
-Virgínia Castillo
-Ricardo Graña
***Natalia S. De Groot, PhD
***Raimon Sabaté, PhD
Special thanks to Proenzymes and Inhibitors Group:
-Josep Vendrell, Prof.
-Irantzu Pallarès, PhD
-Carla Granados
-Montserrat Fàbrega
-Sílvia Llonch