Identifying the amylome, proteins capable of forming amyloid-like fibrils.
The amylome is the universe of proteins that are capable of forming amyloid-like fibrils. Here we investigate the factors that enable a protein to belong to the amylome. A major factor is the presence in the protein of a segment that can form a tightly complementary interface with an identical segment, which permits the formation of a steric zipper-two self-complementary beta sheets that form the spine of an amyloid fibril. Another factor is sufficient conformational freedom of the self-complementary segment to interact with other molecules. Using RNase A as a model system, we validate our fibrillogenic predictions by the 3D profile method based on the crystal structure of NNQQNY and demonstrate that a specific residue order is required for fiber formation. Our genome-wide analysis revealed that self-complementary segments are found in almost all proteins, yet not all proteins form amyloids. The implication is that chaperoning effects have evolved to constrain self-complementary segments from interaction with each other.
Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095-1570, USA.
Lukasz
L
Goldschmidt
Poh K
PK
Teng
Roland
R
Riek
David
D
Eisenberg
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics; D003461:Crystallography; D055106:Genome-Wide Association Study; D018832:Molecular Chaperones / Q000737:chemistry; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000235:genetics; D020539:Sequence Analysis, Protein / Q000379:methods*
D000682:Amyloid; D018832:Molecular Chaperones; D012259:Ribonuclease, Pancreatic