Compartmentalisation driven amyloid assembly 

Abstract

The mechanism of pathological or functional amyloid-assembly is unknown. It is thought that the interaction of proteins with interfaces composed of lipids and/or polysaccharides is essential to amyloid-assembly. In vivo this occurs in overcrowded compartments in which molecular interactions are very different from bulk solution where in-vitro studies are conducted. Herein we will develop a method to entrap proteins and polysaccharides within liposomes to investigate the role of confinement and overcrowding in amyloid-assembly. Biophysical and advanced cryo-electron microscopy techniques will be used to study the mechanism and structure of functional (hormone vasopressin) and pathological (lysozyme) amyloids formed inside the liposomes.




References:
[1]

Maji SK, Perrin MH, Sawaya MR, Jessberger S, Vadodaria K, Rissman RA, Singru PS, Nilsson KP, Simon R, Schubert D, Eisenberg D, Rivier J, Sawchenko P, Vale W, Riek R., Science. 2009 Jul 17;325(5938):328-32. doi: 10.1126/science

[2]

Fabrizio Chiti and Christopher M. Dobson, Annu. Rev. Biochem. 2006. 75:333–66

[3]

A) Milanesi L1, Sheynis T, Xue WF, Orlova EV, Hellewell AL, Jelinek R, Hewitt EW, Radford SE, Saibil HR., Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20455-60. doi: 10.1073/pnas.1206325109; B)Lussignol M., Kopp M., Molloy K., Vizcay G., Fleck R.A., Dorner M., Bell K.L., Chait B.T., Rice C.M., Catanese M.T. (2016). Proteomics of HCV virions reveals an essential role for Nup98 in virus morphogenesis. Proc Natl Acad Sci U S A 2016. 1;113(9), 2484-9.

[4]

Anna Grochmal, Luba Prout, Robert Makin-Taylor, Rafel Prohens, and Salvador Tomas, J. Am. Chem. Soc., 2015, 137 (38), pp 12269–12275

[5]

Sara M. Butterfield and Hilal A. Lashuel, Angew. Chem. Int. Ed. 2010, 49, 5628 – 5654


Biological Areas:

Structural Biology
Chemical Biology

BBSRC Area:

Molecules, cells and industrial biotechnology