期刊
IUCRJ
卷 1, 期 -, 页码 429-438出版社
INT UNION CRYSTALLOGRAPHY
DOI: 10.1107/S2052252514021113
关键词
transthyretin; amyloid assembly; neutron crystallography; deuteration
资金
- EPSRC [GR/R47950/01, GR/R99393/01, EP/C015452/1]
- EU [RII3-CT-2003-505925, NMP4-CT-2006-033256]
- FWF from Austrian Science Fund [P22862]
- Engineering and Physical Sciences Research Council [GR/R99393/01, GR/R47950/01, EP/C015452/1] Funding Source: researchfish
- EPSRC [EP/C015452/1] Funding Source: UKRI
- Austrian Science Fund (FWF) [P22862] Funding Source: Austrian Science Fund (FWF)
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 gamma-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 beta-sheet and the formation of an extended cross-beta structure through sequential dimer couplings. It is argued that the precursor to fibril formation is the dimeric form of the protein.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据