4PVM

Neutron structure of human transthyretin (TTR) at room temperature to 2.0A resolution (Laue)

4PVM の概要

• エントリーDOI: 10.2210/pdb4pvm/pdb
• 関連するPDBエントリー: 2PAB 3IPE 3U2I 4PVL 4PVN
• 分子名称: Transthyretin (2 entities in total)
• 機能のキーワード: beta sandwich, transport protein, serum
• 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

Fisher, S.J.,Blakeley, M.P.,Haupt, M.,Mason, S.A.,Cooper, J.B.,Mitchell, E.P.,Forsyth, V.T. (登録日: 2014-03-18, 公開日: 2014-11-12, 最終更新日: 2024-03-20)

主引用文献

Haupt, M.,Blakeley, M.P.,Fisher, S.J.,Mason, S.A.,Cooper, J.B.,Mitchell, E.P.,Forsyth, V.T.
Binding site asymmetry in human transthyretin: insights from a joint neutron and X-ray crystallographic analysis using perdeuterated protein
IUCrJ, 1:429-438, 2014

PubMed Abstract: Human transthyretin has an intrinsic tendency to form amyloid fibrils and is heavily implicated in senile systemic amyloidosis. Here, detailed neutron structural studies of perdeuterated transthyretin are described. The analyses, which fully exploit the enhanced visibility of isotopically replaced hydrogen atoms, yield new information on the stability of the protein and the possible mechanisms of amyloid formation. Residue Ser117 may play a pivotal role in that a single water molecule is closely associated with the γ-hydrogen atoms in one of the binding pockets, and could be important in determining which of the two sites is available to the substrate. The hydrogen-bond network at the monomer-monomer interface is more extensive than that at the dimer-dimer interface. Additionally, the edge strands of the primary dimer are seen to be favourable for continuation of the β-sheet and the formation of an extended cross-β structure through sequential dimer couplings. It is argued that the precursor to fibril formation is the dimeric form of the protein.

PubMed: 25485123
DOI: 10.1107/S2052252514021113

実験手法

NEUTRON DIFFRACTION (2 Å)
X-RAY DIFFRACTION (1.95 Å)