1uuc: Difference between revisions

The conversion of an alpha-helical to a beta-strand conformation and the, presence of chameleon sequences are fascinating from the perspective that, such structural features are implicated in the induction of, amyloid-related fatal diseases. In this study, we have determined the, solution structure of a chimeric domain (Dom1PI) from the multidomain, Kazal-type serine proteinase inhibitor LEKTI using multidimensional NMR, spectroscopy. This chimeric protein was constructed to investigate the, reasons for differences in the folds of the homologous LEKTI domains 1 and, 6 [Lauber, T., et al. (2003) J. Mol. Biol. 328, 205-219]. In Dom1PI, two, adjacent phenylalanine residues (F28 and F29) of domain 1 were substituted, with proline and isoleucine, respectively, as found in the corresponding, P4' and P5' positions of domain 6. The three-dimensional structure of, Dom1PI is significantly different from the structure of domain 1 and, closely resembles the structure of domain 6, despite the sequence being, identical to that of domain 1 except for the two substituted phenylalanine, residues and being only 31% identical to the sequence of domain 6. The, mutation converted a short 3(10)-helix into an extended loop conformation, and parts of the long COOH-terminal alpha-helix of domain 1 into a, beta-hairpin structure. The latter conformational change occurs in a, sequence stretch distinct from the region containing the substituted, residues. Therefore, this switch from an alpha-helical structure to a, beta-hairpin structure indicates a chameleon sequence of seven residues., We conclude that the secondary structure of Dom1PI is determined not only, by the local protein sequence but also by nonlocal interactions.

1UUC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Structure known Active Site: PP1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UUC OCA].  

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