5NFE

Neutron structure of human transthyretin (TTR) T119M mutant at room temperature to 1.85A resolution

5NFE の概要

• エントリーDOI: 10.2210/pdb5nfe/pdb
• 分子名称: Transthyretin (2 entities in total)
• 機能のキーワード: transthyretin, prealbumin, homotetramer, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28133.56

構造登録者

Yee, A.W.,Moulin, M.,Blakeley, M.P.,Ostermann, A.,Cooper, J.B.,Haertlein, M.,Mitchell, E.P.,Forsyth, V.T. (登録日: 2017-03-14, 公開日: 2019-01-02, 最終更新日: 2024-05-01)

主引用文献

Yee, A.W.,Aldeghi, M.,Blakeley, M.P.,Ostermann, A.,Mas, P.J.,Moulin, M.,de Sanctis, D.,Bowler, M.W.,Mueller-Dieckmann, C.,Mitchell, E.P.,Haertlein, M.,de Groot, B.L.,Boeri Erba, E.,Forsyth, V.T.
A molecular mechanism for transthyretin amyloidogenesis.
Nat Commun, 10:925-925, 2019

PubMed Abstract: Human transthyretin (TTR) is implicated in several fatal forms of amyloidosis. Many mutations of TTR have been identified; most of these are pathogenic, but some offer protective effects. The molecular basis underlying the vastly different fibrillation behaviours of these TTR mutants is poorly understood. Here, on the basis of neutron crystallography, native mass spectrometry and modelling studies, we propose a mechanism whereby TTR can form amyloid fibrils via a parallel equilibrium of partially unfolded species that proceeds in favour of the amyloidogenic forms of TTR. It is suggested that unfolding events within the TTR monomer originate at the C-D loop of the protein, and that destabilising mutations in this region enhance the rate of TTR fibrillation. Furthermore, it is proposed that the binding of small molecule drugs to TTR stabilises non-amyloidogenic states of TTR in a manner similar to that occurring for the protective mutants of the protein.

PubMed: 30804345
DOI: 10.1038/s41467-019-08609-z

実験手法

NEUTRON DIFFRACTION (1.85 Å)
X-RAY DIFFRACTION (1.853 Å)