Exploring the sequence determinants of amyloid structure using position-specific scoring matrices.
Protein aggregation results in beta-sheet-like assemblies that adopt either a variety of amorphous morphologies or ordered amyloid-like structures. These differences in structure also reflect biological differences; amyloid and amorphous beta-sheet aggregates have different chaperone affinities, accumulate in different cellular locations and are degraded by different mechanisms. Further, amyloid function depends entirely on a high intrinsic degree of order. Here we experimentally explored the sequence space of amyloid hexapeptides and used the derived data to build Waltz, a web-based tool that uses a position-specific scoring matrix to determine amyloid-forming sequences. Waltz allows users to identify and better distinguish between amyloid sequences and amorphous beta-sheet aggregates and allowed us to identify amyloid-forming regions in functional amyloids.
VIB SWITCH Laboratory, Flanders Institute for Biotechnology and Vrije Universiteit Brussel, Brussels, Belgium.
Sebastian
S
Maurer-Stroh
Maja
M
Debulpaep
Nico
N
Kuemmerer
Manuela
M
Lopez de la Paz
Ivo Cristiano
IC
Martins
Joke
J
Reumers
Kyle L
KL
Morris
Alastair
A
Copland
Louise
L
Serpell
Luis
L
Serrano
Joost W H
JW
Schymkowitz
Frederic
F
Rousseau
D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D019985:Benchmarking; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
D000682:Amyloid