2gd3

NMR structure of S14G-humanin in 30% TFE solution

Structural highlights

2gd3 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HUNIN_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 PubMed

The NMR solution study of Ser14Gly-humanin (S14G-HN), a 1000-fold more potent derivative of humanin (HN), is reported. HN is 24-residue peptide that selectively suppresses neuronal cell death caused by Alzheimer's disease (AD)-specific insults and offers hope for the development of a cure against AD. In aqueous solution the NMR data show that S14G-HN is a flexible peptide with turn-like structures in its conformational ensemble distributed over an extensive part of its sequence from Pro3 to Glu15. In the more lipophilic environment of 30% TFE, an alpha-helical structure spanning residues Phe6 to Thr13 is identified. Comparison of these findings to the NMR structure of the parent HN and to existing structure-function relationship literature data outlines the important for activity structural features for this class of neuroprotective peptides, and brings forth flexibility as an important characteristic that may facilitate interactions with functional counterparts of the neuroprotection pathway.

Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer's disease.,Benaki D, Zikos C, Evangelou A, Livaniou E, Vlassi M, Mikros E, Pelecanou M Biochem Biophys Res Commun. 2006 Oct 20;349(2):634-42. Epub 2006 Aug 23. PMID:16945331^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41. PMID:11371646 doi:10.1073/pnas.101133498
↑ Ikonen M, Liu B, Hashimoto Y, Ma L, Lee KW, Niikura T, Nishimoto I, Cohen P. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13042-7. Epub 2003 Oct 15. PMID:14561895 doi:https://dx.doi.org/10.1073/pnas.2135111100
↑ Hashimoto Y, Niikura T, Ito Y, Sudo H, Hata M, Arakawa E, Abe Y, Kita Y, Nishimoto I. Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults. J Neurosci. 2001 Dec 1;21(23):9235-45. PMID:11717357
↑ Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003 May 22;423(6938):456-61. Epub 2003 May 4. PMID:12732850 doi:https://dx.doi.org/10.1038/nature01627
↑ Ying G, Iribarren P, Zhou Y, Gong W, Zhang N, Yu ZX, Le Y, Cui Y, Wang JM. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol. 2004 Jun 1;172(11):7078-85. PMID:15153530
↑ Benaki D, Zikos C, Evangelou A, Livaniou E, Vlassi M, Mikros E, Pelecanou M. Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer's disease. Biochem Biophys Res Commun. 2006 Oct 20;349(2):634-42. Epub 2006 Aug 23. PMID:16945331 doi:S0006-291X(06)01881-X

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41. PMID:11371646 doi:10.1073/pnas.101133498

[2] Ikonen M, Liu B, Hashimoto Y, Ma L, Lee KW, Niikura T, Nishimoto I, Cohen P. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13042-7. Epub 2003 Oct 15. PMID:14561895 doi:https://dx.doi.org/10.1073/pnas.2135111100

[3] Hashimoto Y, Niikura T, Ito Y, Sudo H, Hata M, Arakawa E, Abe Y, Kita Y, Nishimoto I. Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults. J Neurosci. 2001 Dec 1;21(23):9235-45. PMID:11717357

[4] Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003 May 22;423(6938):456-61. Epub 2003 May 4. PMID:12732850 doi:https://dx.doi.org/10.1038/nature01627

[5] Ying G, Iribarren P, Zhou Y, Gong W, Zhang N, Yu ZX, Le Y, Cui Y, Wang JM. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol. 2004 Jun 1;172(11):7078-85. PMID:15153530

[6] Benaki D, Zikos C, Evangelou A, Livaniou E, Vlassi M, Mikros E, Pelecanou M. Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer's disease. Biochem Biophys Res Commun. 2006 Oct 20;349(2):634-42. Epub 2006 Aug 23. PMID:16945331 doi:S0006-291X(06)01881-X

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2gd3

NMR structure of S14G-humanin in 30% TFE solution

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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