サイエンス記事
トランスサイレチンにおける水素結合ネットワークとpH感受性
2013 年 23 巻 2 号 p. 142-145
詳細
2013 年 23 巻 2 号 p. 142-145
The human amyloid disorders, familial amyloid polyneuropathy and senile systemic amyloidosis are caused by insoluble transthyretin (TTR). Dissociation of the TTR tetramer appears to be the rate-determining step in amyloid cascade and the formation of amyloid fibrils is known to be promoted by lowered pH. In order to reveal the molecular mechanisms of the pH sensitivity and structural stabilities of TTR, neutron diffraction studies were conducted using IBARAKI Biological Crystal Diffractometer at J-PARC. The neutron structure solved at 2.0 Å revealed the protonation states of His88 and the detailed hydrogen-bond network depending on the protonation states of His88. This hydrogen-bond network is involved in monomer-monomer and dimer-dimer interactions, suggesting that the double protonation of His88 by acidification breaks the hydrogen-bond network and causes the destabilization of TTR.
