 |
|
|
 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
59 a.a.
Key reference
DOI no: 10.1021/bi0492399 Biochemistry 43:11238-11247 (2004) PubMed id: 15366933
The solution structure of a chimeric LEKTI domain reveals a chameleon sequence. H.Tidow, T.Lauber, K.Vitzithum, C.P.Sommerhoff, P.Rösch, U.C.Marx. 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.
Literature references that cite this PDB file's key reference
PubMed id Reference
18287054 A.R.Davidson (2008).
A folding space odyssey.Proc Natl Acad Sci U S A, 105, 2759-2760.
17299764 J.T.Guo, J.W.Jaromczyk, and Y.Xu (2007).
Analysis of chameleon sequences and their implications in biological processes.Proteins, 67, 548-558.
16307483 N.M.Schechter, E.J.Choi, Z.M.Wang, Y.Hanakawa, J.R.Stanley, Y.Kang, G.L.Clayman, and A.Jayakumar (2005).
Inhibition of human kallikreins 5 and 7 by the serine protease inhibitor lympho-epithelial Kazal-type inhibitor (LEKTI).Biol Chem, 386, 1173-1184. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.
 |