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.
Maurer-Stroh
Sebastian
S
VIB SWITCH Laboratory, Flanders Institute for Biotechnology and Vrije Universiteit Brussel, Brussels, Belgium.
Debulpaep
Maja
M
Kuemmerer
Nico
N
Lopez de la Paz
Manuela
M
Martins
Ivo Cristiano
IC
Reumers
Joke
J
Morris
Kyle L
KL
Copland
Alastair
A
Serpell
Louise
L
Serrano
Luis
L
Schymkowitz
Joost W H
JW
Rousseau
Frederic
F
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