Proteins that convert from alpha helix to beta sheet: implications for folding and disease.
The sequence of a protein normally determines which amino acid residues will form alpha helices, and which one beta sheets, to an extent that allows secondary structure prediction to be made with a reasonable reliability. Nevertheless, non-native helical structures are observed during in vitro folding of several model proteins and may even occur during protein biosynthesis within the ribosomal exit tunnel. Moreover, non-native beta sheet structures are common in amyloid fibrils formed by a variety of pathogenic and even non-pathogenic proteins and peptides. In all of these cases, the formation of alpha helix precedes the appearance of beta sheet, which suggests that conversion from the simpler, more local helix structure to the often more convoluted sheet architecture during folding and pathogenic misfolding processes could be a unifying principle of general importance. A better understanding of this switching process, and the ability to design molecular systems which can be induced to switch between these conformations will have a significant impact on fields ranging from fundamental biochemistry through to applied technology and medicine.
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D018832:Molecular Chaperones