Identifying the amylome, proteins capable of forming amyloid-like fibrils

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010-02, Vol.107 (8), p.3487-3492
• Main Authors: Goldschmidt, Lukasz, Teng, Poh K, Riek, Roland, Eisenberg, David
• Format: Article
• Language: English
• Subjects: Aggregation; Amino Acid Sequence; Amyloid - chemistry; Amyloid - genetics; Amyloids; Biological Sciences; Crystallography; Datasets; Fibrillation; Genome-Wide Association Study; Genomes; Genomics; Globulins; Molecular Chaperones - chemistry; Molecular Sequence Data; Molecular structure; Molecules; Open reading frames; Protein Folding; Protein Structure, Secondary; Proteins; Ribonuclease, Pancreatic - chemistry; Ribonuclease, Pancreatic - genetics; Sequence Analysis, Protein - methods; Solar fibrils; Solvents; Spine
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0915166107

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.