5GIW

Solution NMR structure of Humanin containing a D-isomerized serine residue

5GIW の概要

• エントリーDOI: 10.2210/pdb5giw/pdb
• NMR情報: BMRB: 36009
• 分子名称: Humanin (1 entity in total)
• 機能のキーワード: d-ser, alzheimer disease, apoptosis
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted : Q8IVG9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2691.26

構造登録者

Furuita, K.,Sugiki, T.,Alsanousi, N.,Fujiwara, T.,Kojima, C. (登録日: 2016-06-25, 公開日: 2016-07-20, 最終更新日: 2024-11-13)

主引用文献

Alsanousi, N.,Sugiki, T.,Furuita, K.,So, M.,Lee, Y.H.,Fujiwara, T.,Kojima, C.
Solution NMR structure and inhibitory effect against amyloid-beta fibrillation of Humanin containing a d-isomerized serine residue
Biochem.Biophys.Res.Commun., 477:647-653, 2016

PubMed Abstract: Humanin comprising 24 amino acid residues is a bioactive peptide that has been isolated from the brain tissue of patients with Alzheimer's disease. Humanin reportedly suppressed aging-related death of various cells due to amyloid fibrils and oxidative stress. There are reports that the cytoprotective activity of Humanin was remarkably enhanced by optical isomerization of the Ser14 residue from l to d form, but details of the molecular mechanism remained unclear. Here we demonstrated that Humanin d-Ser14 exhibited potent inhibitory activity against fibrillation of amyloid-β and remarkably higher binding affinity for amyloid-β than that of the Humanin wild-type and S14G mutant. In addition, we determined the solution structure of Humanin d-Ser14 by nuclear magnetic resonance (NMR) and showed that d-isomerization of the Ser14 residue enables drastic conformational rearrangement of Humanin. Furthermore, we identified an amyloid-β-binding site on Humanin d-Ser14 at atomic resolution by NMR. These biophysical and high-resolution structural analyses clearly revealed structure-function relationships of Humanin and explained the driving force of the drastic conformational change and molecular basis of the potent anti-amyloid-β fibrillation activity of Humanin caused by d-isomerization of the Ser14 residue. This is the first study to show correlations between the functional activity, tertiary structure, and partner recognition mode of Humanin and may lead to elucidation of the molecular mechanisms of the cytoprotective activity of Humanin.

PubMed: 27349871
DOI: 10.1016/j.bbrc.2016.06.114

実験手法

SOLUTION NMR