1UVG

Solution structure of the 15th Domain of LEKTI

Summary for 1UVG

• Entry DOI: 10.2210/pdb1uvg/pdb
• Related: 1H0Z 1HDL 1UUC 1UVF
• NMR Information: BMRB: 6180
• Descriptor: SERINE PROTEINASE INHIBITOR KAZAL TYPE 5 (1 entity in total)
• Functional Keywords: serine proteinase inhibitor, trypsin inhibitor, kazal, protease
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 8585.64

Authors

Vitzithum, K.,Roesch, P.,Marx, U.C. (deposition date: 2004-01-20, release date: 2005-04-14, Last modification date: 2024-10-09)

Primary citation

Tidow, H.,Lauber, T.,Vitzithum, K.,Sommerhoff, C.,Roesch, P.,Marx, U.C.
The Solution Structure of a Chimeric Lekti Domain Reveals a Chameleon Sequence
Biochemistry, 43:11238-, 2004

PubMed Abstract: 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.

PubMed: 15366933
DOI: 10.1021/BI0492399

Experimental method

SOLUTION NMR