Ali Javanmard, Maryam Azimzadeh-Irani, Ghazal Tafazzoli, Ayla Esmaeilzadeh, Mohammad Shirinpoor-Kharf, Seyyed Mohammad Hasan Haghayeghi
{"title":"In-silico structural analysis of <i>Heterocephalus glaber</i> amyloid beta: an anti-Alzheimer's peptide.","authors":"Ali Javanmard, Maryam Azimzadeh-Irani, Ghazal Tafazzoli, Ayla Esmaeilzadeh, Mohammad Shirinpoor-Kharf, Seyyed Mohammad Hasan Haghayeghi","doi":"10.22099/mbrc.2023.48223.1862","DOIUrl":null,"url":null,"abstract":"<p><p><i>Heterocephalus glaber</i>, known as the Naked mole-rat, has an extraordinary immunity to Alzheimer's disease. The pathological hallmark of Alzheimer's disease is cerebral accumulations of plaques, consisting of self-aggregated amyloid beta peptides. <i>Homo sapiens</i> and <i>H. glaber</i> amyloid beta peptides are different in only one amino acid. Herein, computational structural analyses were carried out to determine whether plaque development in <i>H. glaber</i> is prevented by the replacement of His13 with Arg13 in the amyloid beta peptide. AlphaFold2 was used to predict the structure of the <i>H. glaber</i> amyloid beta peptide. HADDOCK and Hex were used to self-dock the peptides and dock ions on peptides, respectively. Illustrations were made by PyMol and ChimeraX. Using VMD, we calculated the radius of gyration. The phylogenetic analysis was conducted by Mega. The results showed an accurate structure with two alpha helices separated by a short coil for <i>H. glaber</i>. Self-docking of the two amyloid beta peptides demonstrated a globular conformation in the <i>H. glaber</i> dimer, implying the unlikeliness of amyloid beta peptides' self-aggregation to form fibrillar structures. This conformational state resulted in lower electrostatic energy compared to <i>H. sapiens</i>, contributing to <i>H. glaber's</i> lower tendency for fibril and, ultimately, plaque formation. Phylogenetic analysis confirmed that amyloid precursor protein is highly conserved in each taxon of rodentia and primata. This study provides insight into the connection between the structure of <i>H. glaber</i> amyloid beta and its plaque formation properties, showing that the Arg13 in <i>H. glaber</i> leads to fibril instability, and might prevent senile plaque accumulation.</p>","PeriodicalId":19025,"journal":{"name":"Molecular Biology Research Communications","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644309/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Biology Research Communications","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.22099/mbrc.2023.48223.1862","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Heterocephalus glaber, known as the Naked mole-rat, has an extraordinary immunity to Alzheimer's disease. The pathological hallmark of Alzheimer's disease is cerebral accumulations of plaques, consisting of self-aggregated amyloid beta peptides. Homo sapiens and H. glaber amyloid beta peptides are different in only one amino acid. Herein, computational structural analyses were carried out to determine whether plaque development in H. glaber is prevented by the replacement of His13 with Arg13 in the amyloid beta peptide. AlphaFold2 was used to predict the structure of the H. glaber amyloid beta peptide. HADDOCK and Hex were used to self-dock the peptides and dock ions on peptides, respectively. Illustrations were made by PyMol and ChimeraX. Using VMD, we calculated the radius of gyration. The phylogenetic analysis was conducted by Mega. The results showed an accurate structure with two alpha helices separated by a short coil for H. glaber. Self-docking of the two amyloid beta peptides demonstrated a globular conformation in the H. glaber dimer, implying the unlikeliness of amyloid beta peptides' self-aggregation to form fibrillar structures. This conformational state resulted in lower electrostatic energy compared to H. sapiens, contributing to H. glaber's lower tendency for fibril and, ultimately, plaque formation. Phylogenetic analysis confirmed that amyloid precursor protein is highly conserved in each taxon of rodentia and primata. This study provides insight into the connection between the structure of H. glaber amyloid beta and its plaque formation properties, showing that the Arg13 in H. glaber leads to fibril instability, and might prevent senile plaque accumulation.
期刊介绍:
“Molecular Biology Research Communications” (MBRC) is an international journal of Molecular Biology. It is published quarterly by Shiraz University (Iran). The MBRC is a fully peer-reviewed journal. The journal welcomes submission of Original articles, Short communications, Invited review articles, and Letters to the Editor which meets the general criteria of significance and scientific excellence in all fields of “Molecular Biology”.