1ZD6

Crystal structure of human transthyretin with bound chloride

1ZD6 の概要

• エントリーDOI: 10.2210/pdb1zd6/pdb
• 関連するPDBエントリー: 1ZCR 1f41
• 分子名称: Transthyretin, CHLORIDE ION (3 entities in total)
• 機能のキーワード: transport, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28029.83

構造登録者

Hornberg, A.,Hultdin, U.W.,Olofsson, A.,Sauer-Eriksson, A.E. (登録日: 2005-04-14, 公開日: 2005-07-12, 最終更新日: 2024-03-13)

主引用文献

Hornberg, A.,Hultdin, U.W.,Olofsson, A.,Sauer-Eriksson, A.E.
The effect of iodide and chloride on transthyretin structure and stability
Biochemistry, 44:9290-9299, 2005

PubMed Abstract: Transthyretin amyloid formation occurs through a process of tetramer destabilization and partial unfolding. Small molecules, including the natural ligand thyroxine, stabilize the tetrameric form of the protein, and serve as inhibitors of amyloid formation. Crucial for TTR's ligand-binding properties are its three halogen-binding sites situated at the hormone-binding channel. In this study, we have performed a structural characterization of the binding of two halides, iodide and chloride, to TTR. Chlorides are known to shield charge repulsions at the tetrameric interface of TTR, which improve tetramer stability of the protein. Our study shows that iodides, like chlorides, provide tetramer stabilization in a concentration-dependent manner and at concentrations approximately 15-fold below that of chlorides. To elucidate binding sites of the halides, we took advantage of the anomalous scattering of iodide and used the single-wavelength anomalous dispersion (SAD) method to solve the iodide-bound TTR structure at 1.8 A resolution. The structure of chloride-bound TTR was determined at 1.9 A resolution using difference Fourier techniques. The refined structures showed iodides and chlorides bound at two of the three halogen-binding sites located at the hydrophobic channel. These sites therefore also function as halide-binding sites.

PubMed: 15981995
DOI: 10.1021/bi050249z

実験手法

X-RAY DIFFRACTION (1.9 Å)