Synthesis and structural analysis of the N-terminal domain of the thyroid hormone-binding protein transthyretin

Wilce, Jackie A., Daly, Norelle L. and Craik, David J. (2002) Synthesis and structural analysis of the N-terminal domain of the thyroid hormone-binding protein transthyretin. Clinical Chemistry And Laboratory Medicine, 40 12: 1221-1228. doi:10.1515/CCLM.2002.212

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ64165_OA.pdf Full text (open access) application/pdf 151.90KB 0

Author Wilce, Jackie A.
Daly, Norelle L.
Craik, David J.
Title Synthesis and structural analysis of the N-terminal domain of the thyroid hormone-binding protein transthyretin
Journal name Clinical Chemistry And Laboratory Medicine   Check publisher's open access policy
ISSN 1434-6621
Publication date 2002
Sub-type Article (original research)
DOI 10.1515/CCLM.2002.212
Open Access Status File (Publisher version)
Volume 40
Issue 12
Start page 1221
End page 1228
Total pages 8
Place of publication Berlin
Publisher Walter De Gruyter
Collection year 2002
Language eng
Subject C1
250302 Biological and Medical Chemistry
670403 Treatments (e.g. chemicals, antibiotics)
Abstract Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and retinol in human serum. Misfolded forms of the protein are implicated in the amyloid diseases familial amyloidotic polyneuropathy and senile systemic amyloidosis. Its folding properties and stabilization by ligands are of current interest due to their importance in understanding and combating these diseases. To assist in such studies we developed a method for the solid phase synthesis of the monomeric unit of a TTR analogue and its folding to form a functional 55 kDa tetramer. The monomeric unit of the protein was chemically synthesized in three parts, comprising amino acid residues 151, 5499 and 102127, and ligated using chemoselective thioether ligation chemistry. The synthetic protein was folded and assembled to a tetrameric structure in the presence of the TTRs native ligand, thyroxine, as shown by gel filtration chromatography, native gel electrophoresis, TTR antibody recognition and thyroid hormone binding. In the current study the solution structure of the first of these fragment peptides, TTR(151) is examined to determine its intrinsic propensity to form beta-sheet structure, potentially involved in amyloid fibril formation by TTR. Despite the presence of extensive beta-structure in the native form of the protein, the Nterminal fragment adopts an essentially random coil conformation in solution.
Keyword Medical Laboratory Technology
Peptide Synthesis
Protein Fragments
Transthyretin
Amyloid
Amyloid Fibril Formation
X-ray-diffraction
Peptide-fragments
Thyroxine-binding
Nmr-spectroscopy
T4 Lysozyme
Disease
Resolution
Inhibitors
Variant
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 1 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 14 Aug 2007, 18:58:18 EST