The solution structure of a chimeric LEKTI domain reveals a chameleon sequence

Biochemistry
Henning TidowUte 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-ter...Continue Reading

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Citations

Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alan R Davidson
Jun 17, 2011·Protein Engineering, Design & Selection : PEDS·William J AndersonMatthew H J Cordes
Oct 20, 2010·BMC Bioinformatics·Nicholus Bhattacharjee, Parbati Biswas
May 17, 2013·BMC Structural Biology·Nicholus Bhattacharjee, Parbati Biswas
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Mar 24, 2016·The Journal of Physical Chemistry. B·Bongkeun KimJoan-Emma Shea
Jan 24, 2007·Current Biology : CB·Todd O Yeates
Aug 29, 2019·Chembiochem : a European Journal of Chemical Biology·Héctor Zamora-CarrerasM Angeles Jiménez
May 21, 2015·Protein Engineering, Design & Selection : PEDS·Karen V EatonMatthew H J Cordes

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