論文 - 詳細
| RRC ID | 67291 |
|---|---|
| 著者 | Sebastian Samuel J, Kumar D, Chodisetti SB, Agrewala JN, Singh B, Guptasarma P, Sarkar D. |
| タイトル | Probing protease sensitivity of recombinant human erythropoietin reveals α3-α4 inter-helical loop as a stability determinant. |
| ジャーナル | Proteins |
| Abstract |
Although unglycosylated HuEpo is fully functional, it has very short serum half-life. However, the mechanism of in vivo clearance of human Epo (HuEpo) remains largely unknown. In this study, the relative importance of protease-sensitive sites of recombinant HuEpo (rHuEpo) has been investigated by analysis of structural data coupled with in vivo half-life measurements. Our results identify α3-α4 inter-helical loop region as a target site of lysosomal protease Cathepsin L. Consistent with previously-reported lysosomal degradation of HuEpo, these results for the first time identify cleavage sites of rHuEpo by specific lysosomal proteases. Furthermore, in agreement with the lowered exposure of the peptide backbone around the cleavage site, remarkably substitutions of residues with bulkier amino acids result in significantly improved in vivo stability. Together, these results have implications for the mechanism of in vivo clearance of the protein in humans. |
| 巻・号 | 83(10) |
| ページ | 1813-22 |
| 公開日 | 2015-10-1 |
| DOI | 10.1002/prot.24865 |
| PMID | 26214268 |
| MeSH | Amino Acid Sequence Cathepsin L / metabolism Cell Line, Tumor Erythropoietin / chemistry* Erythropoietin / metabolism Humans Molecular Dynamics Simulation Molecular Sequence Data Protein Stability Protein Structure, Secondary Recombinant Proteins / chemistry* Recombinant Proteins / metabolism |
| IF | 2.828 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | F-36E(RCB0776) |