1uuc

From Proteopedia

Revision as of 15:06, 5 November 2007

SOLUTION STRUCTURE OF A CHIMERIC LEKTI-DOMAIN

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.

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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