A strand-loop-strand structure is a possible intermediate in fibril   elongation: Long time simulations of amylold-beta peptide (10-35)

doi:10.1021/ja051699h

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	A strand-loop-strand structure is a possible intermediate in fibril elongation: Long time simulations of amylold-beta peptide (10-35)
	Han, W ; Wu, YD
刊名	journal of the american chemical society
	2005
关键词	MOLECULAR-DYNAMICS SIMULATIONS E22Q DUTCH MUTANT SOLID-STATE NMR ALZHEIMERS-DISEASE WATER MODELS IN-VITRO PROTEIN AGGREGATION PLAQUE COMPETENCE NUCLEATION MECHANISM
DOI	10.1021/ja051699h
英文摘要	A total of 6.2 mu s molecular dynamics simulations of amyloid-beta (10-35) (A beta) were performed in explicit water solvent. The results reveal that the collapsed-coil (cc) structure determined by experiments is stable at pH 5.6 for hundreds of nanoseconds, but it can exchange with a strand-loop-strand (SLS) structure on the microsecond time scale. The SLS structure has D23-K28 as a reverse loop and the central hydrophobic core and the C-terminal in hydrophobic contact. This SLS structure topologically resembles the proposed monomer conformation in fibrils. Since it has been suggested that a special conformation of A beta is needed when the monomer binds to fibril ends to elongate fibrils, we propose that the SLS structure may be an important intermediate binding structure for A beta fibril growth. Simulations at pH 2.0, which is used to mimic the mutation of E22Q and D23N, and at high temperature (400 K) indicate that the SLS structure is considerably populated under these conditions while the cc structure is disrupted. These results imply that the SLS structures may also be a binding intermediate in other conditions such as E22Q and/or D23N mutations and high temperature, which have been proved to promote fibril formation previously.; Chemistry, Multidisciplinary; SCI(E); EI; 0; ARTICLE; 44; 15408-15416; 127
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/253709]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Han, W,Wu, YD. A strand-loop-strand structure is a possible intermediate in fibril elongation: Long time simulations of amylold-beta peptide (10-35)[J]. journal of the american chemical society,2005.
APA	Han, W,&Wu, YD.(2005).A strand-loop-strand structure is a possible intermediate in fibril elongation: Long time simulations of amylold-beta peptide (10-35).journal of the american chemical society.
MLA	Han, W,et al."A strand-loop-strand structure is a possible intermediate in fibril elongation: Long time simulations of amylold-beta peptide (10-35)".journal of the american chemical society (2005).