Premium
Location and Conformation of Amyloid β(25–35) Peptide and its Sequence‐Shuffled Peptides within Membranes: Implications for Aggregation and Toxicity in PC12 Cells
Author(s) -
Tsai HuiHsu Gavin,
Lee JianBin,
Shih YuanCi,
Wan Lei,
Shieh FaKuen,
Chen ChinYu
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201400062
Subject(s) - membrane , peptide , sequence (biology) , chemistry , biophysics , molecular dynamics , amyloid (mycology) , extracellular , peptide sequence , neurotoxicity , folding (dsp implementation) , biochemistry , toxicity , biology , computational chemistry , organic chemistry , inorganic chemistry , gene , electrical engineering , engineering
Extracellular deposits of amyloid β (Aβ) aggregates in the brain is the hallmark of Alzheimer’s disease. We present the configurations (location and conformation) and the interfacial folding and membrane insertion mechanisms of Aβ fragments, wild‐type Aβ(25–35), Aβ(35–25), and a sequence‐shuffled peptide [Aβ(25–35)‐shuffled] from Aβ(25–35) within membranes by replica‐exchange molecular dynamics simulations. Although these peptides have the same amino acid composition, simulations show they have distinct locations and conformations within membranes. Moreover, our in vitro experiments show that these peptides have distinct neurotoxicities. We rationalize the distinct neurotoxicities of these peptides in terms of their simulated locations and conformations in membranes. This work provides another view that complements the general hydrophobicity–toxicity views, to better explain the neurotoxicity of Aβ peptides.