5CNH

X-ray structure of perdeuterated wild-type TTR at 1.42A resolution

5CNH の概要

• エントリーDOI: 10.2210/pdb5cnh/pdb
• 関連するPDBエントリー: 5CN3
• 分子名称: Transthyretin (2 entities in total)
• 機能のキーワード: ttr, attr, prealbumin, 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: 28073.38

構造登録者

Yee, A.W.,Moulin, M.,Mossou, E.,Haertlein, M.,Mitchell, E.P.,Cooper, J.B.,Forsyth, V.T. (登録日: 2015-07-17, 公開日: 2016-07-06, 最終更新日: 2024-01-10)

主引用文献

Yee, A.W.,Moulin, M.,Breteau, N.,Haertlein, M.,Mitchell, E.P.,Cooper, J.B.,Boeri Erba, E.,Forsyth, V.T.
Impact of Deuteration on the Assembly Kinetics of Transthyretin Monitored by Native Mass Spectrometry and Implications for Amyloidoses.
Angew.Chem.Int.Ed.Engl., 55:9292-9296, 2016

PubMed Abstract: It is well established that the formation of transthyretin (TTR) amyloid fibrils is linked to the destabilization and dissociation of its tetrameric structure into insoluble aggregates. Isotope labeling is used for the study of TTR by NMR, neutron diffraction, and mass spectrometry (MS). Here MS, thioflavin T fluorescence, and crystallographic data demonstrate that while the X-ray structures of unlabeled and deuterium-labeled TTR are essentially identical, subunit exchange kinetics and amyloid formation are accelerated for the deuterated protein. However, a slower subunit exchange is noted in deuterated solvent, reflecting the poorer solubility of non-polar protein side chains in such an environment. These observations are important for the interpretation of kinetic studies involving deuteration. The destabilizing effects of TTR deuteration are rather similar in character to those observed for aggressive mutations of TTR such as L55P (associated with familial amyloid polyneuropathy).

PubMed: 27311939
DOI: 10.1002/anie.201602747

実験手法

X-RAY DIFFRACTION (1.42 Å)