5giw
From Proteopedia
Solution NMR structure of Humanin containing a D-isomerized serine residue
Structural highlights
FunctionHUNIN_HUMAN Plays a role as a neuroprotective factor. Protects against death induced by multiple different familial Alzheimer disease genes and beta amyloid proteins in Alzheimer disease. Suppresses apoptosis by binding to BAX and preventing the translocation of BAX from the cytosol to mitochondria. Binds to IGFBP3 and specifically blocks IGFBP3-induced cell death Induces chemotaxis of mononuclear phagocytes via FPR2. Reduces the aggregation and fibrillary formation by suppressing the effect of APP on mononuclear phagocytes and acts by competitively inhibiting the access of FPRL1 to APP.[1] [2] [3] [4] [5] Publication Abstract from PubMedHumanin 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-beta and remarkably higher binding affinity for amyloid-beta 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-beta-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-beta 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. Solution NMR structure and inhibitory effect against amyloid-beta fibrillation of Humanin containing a d-isomerized serine residue.,Alsanousi N, Sugiki T, Furuita K, So M, Lee YH, Fujiwara T, Kojima C Biochem Biophys Res Commun. 2016 Jun 25. pii: S0006-291X(16)31032-4. doi:, 10.1016/j.bbrc.2016.06.114. PMID:27349871[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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