PREDICTION OF FIBRIL CORE REGIONS IN AMYLOID FORMING PROTEINS

摘要

The formations of amyloid fibrils have been reported for various amyloidosis. Up to date several structural models of fibrils are proposed for respective proteins. However, their common basic structures and universal features to induce amyloid fibril formations are not known in detail. Previously, we examined intermolecular interactions among the several amino acid residues in barnase, of which is known to form amyloid-like fibril. Based on the experimental results using a series of mutant barnase, we have succeeded in identifying the essential interactions for amyloid formation. The results indicated that the most essential interaction is the hydrophobic interaction between amino acid residues effectively operating in inter-strand, inter-molecular, and inter-sheet manners, as shown in Fig.1. In the present paper, we describe a novel prediction method for core regions of various fibril-forming proteins and show the verification of the assumption that the fibril formation is caused by the alignment of hydrophobic residues and hydrogen-bonding side-chains in the direction of fibril axis.