Naked Mole-Rat, a Rodent with an Apolipoprotein A-I Dimer
| Autor: | Muhammad A. Zenaidee, Rochelle Buffenstein, Sarada Charugundla, Don L. Puppione, Denise P. Tran, Julian P. Whitelegge |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Models Molecular Apolipoprotein B Dimer Biochemistry Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Species Specificity polycyclic compounds Animals Cysteine Databases Protein Gene Naked mole-rat chemistry.chemical_classification 030109 nutrition & dietetics biology Apolipoprotein A-I Organic Chemistry nutritional and metabolic diseases Heterozygote advantage Cell Biology biology.organism_classification Amino acid Rats 030104 developmental biology chemistry biology.protein lipids (amino acids peptides and proteins) Protein Multimerization Lipoproteins HDL Chromatography Liquid Protein Binding |
| Zdroj: | LipidsReferences. 56(3) |
| ISSN: | 1558-9307 |
| Popis: | A variety of rodents have been used as experimental animals in metabolic studies of plasma lipids and lipoproteins. These studies have included understanding the functional role of apolipoprotein A-I, the major protein on the surface of HDL. Reviewing the genomic database for entries for rodent apoA-I genes, it was discovered that the naked mole-rat (Heterocephalus glaber) gene encoded a protein with a cysteine at residue 28. Previously, two cases have been reported in which human heterozygotes had apoA-I with cysteine at residues 173 (apoA-I Milano) or at 151 (apoA-I Paris). Interestingly, both groups, in spite of having low levels of HDL and moderately elevated plasma triacylglycerols, had no evidence of cardiovascular disease. Moreover, the presence of the cysteine enabled the apoA-I to form both homodimers and heterodimers. Prior to this report, no other mammalian apoA-I has been found with a cysteine in its sequence. In addition, the encoded naked mole-rat protein had different amino acids at sites that were conserved in all other mammals. These differences resulted in naked mole-rat apoA-I having an unexpected neutral pI value, whereas other mammalian apoA-I have negative pI values. To verify these sequence differences and to determine if the N-terminal location of C28 precluded dimer formation, we conducted mass spectrometry analyses of apoA-I and other proteins associated with HDL. Consistent with the genomic data, our analyses confirmed the presence of C28 and the formation of a homodimer. Analysis of plasma lipids surprisingly revealed a profile similar to the human heterozygotes. |
| Databáze: | OpenAIRE |
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