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

Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095-1570, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 02/2010; 107(8):3487-92. DOI: 10.1073/pnas.0915166107
Source: PubMed

ABSTRACT 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.

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