1uuc
From Proteopedia
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==Overview== | ==Overview== | ||
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. | 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. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Atopy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605010 605010]], Netherton syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605010 605010]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: serine proteinase inhibitor]] | [[Category: serine proteinase inhibitor]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:38:47 2007'' |
Revision as of 17:32, 12 November 2007
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SOLUTION STRUCTURE OF A CHIMERIC LEKTI-DOMAIN
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Atopy OMIM:[605010], Netherton syndrome OMIM:[605010]
About this Structure
1UUC is a Single protein structure of sequence from Homo sapiens. Structure known Active Site: PP1. Full crystallographic information is available from OCA.
Reference
The solution structure of a chimeric LEKTI domain reveals a chameleon sequence., Tidow H, Lauber T, Vitzithum K, Sommerhoff CP, Rosch P, Marx UC, Biochemistry. 2004 Sep 7;43(35):11238-47. PMID:15366933
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