1QCM

AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES

1QCM の概要

• エントリーDOI: 10.2210/pdb1qcm/pdb
• 分子名称: AMYLOID BETA PEPTIDE (1 entity in total)
• 機能のキーワード: glycoprotein, amyloid, alzheimer's disease, down's syndrome, neurone, transmembrane, alternative splicing, serine protease inhibitor, disease mutation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05067
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1061.28

構造登録者

Kohno, T.,Kobayashi, K.,Maeda, T.,Sato, K.,Takashima, A. (登録日: 1996-07-19, 公開日: 1997-07-07, 最終更新日: 2024-05-22)

主引用文献

Kohno, T.,Kobayashi, K.,Maeda, T.,Sato, K.,Takashima, A.
Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment.
Biochemistry, 35:16094-16104, 1996

PubMed Abstract: The three-dimensional structure of amyloid beta peptide (25-35), which has neurotoxic activity, in lithium dodecyl sulfate micelles was determined by two-dimensional 1H NMR spectroscopy with simulated annealing calculations. A total of 20 converged amyloid beta peptide structures were obtained on the basis of 110 experimental constraints, including 106 distance constraints reduced from the nuclear Overhauser effect (NOE) connectivities and four torsion angle (phi) constraints. The atomic root mean square difference about averaged coordinates is 1.04 +/- 0.25 A for the backbone atoms (N, C alpha, C) and 1.39 +/- 0.27 A for all heavy atoms of the entire peptide. The molecular structure of amyloid beta peptide in membrane-mimicking environment is composed of a short alpha helix in the C terminal position. The three residues from the N-terminus are disordered, but the remaining eight C-terminal residues are well-ordered, which is supported by the RMSD values of the C-terminal region, Lys28-Leu34. In this region, the RMS differences from averaged coordinates are 0.26 +/- 0.11 A for the backbone atoms (N, C alpha, C) and 0.77 +/- 0.21 A for all heavy atoms, which is very low compared with those for the entire peptide. The four amino acid residues from the N-terminus are hydrophilic and the other seven amino acid residues in C-terminus are hydrophobic. So, our results show that the C-terminal region of amyloid beta peptide (25-35) is buried in the membrane and assumes alpha-helical structure, whereas the N-terminal region is exposed to the solvent with a flexible structure. This structure is very similar to membrane-mediated structure of substance P previously reported. The three-dimensional structure of a non-neurotoxic mutant of amyloid beta peptide (25-35), where Asn27 is replaced by Ala, in lithium dodecyl sulfate micelles was also determined. The structure is similar to that of the wild type amyloid beta peptide (25-35) in the C-terminal region, but the N-terminal flexible region is different. The structural comparison of amyloid beta peptide (25-35), its non-neurotoxic mutant and substance P gives a structural basis to understand the mechanism of neurotoxicity caused by amyloid beta peptide.

PubMed: 8973180
DOI: 10.1021/bi961598j

実験手法

SOLUTION NMR