6QMN

Crystal structure of a Ribonuclease A-Onconase chimera

6QMN の概要

• エントリーDOI: 10.2210/pdb6qmn/pdb
• 分子名称: Ribonuclease pancreatic, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: pancreatic ribonuclease a, alpha/beta fold, chimera, hydrolase
• 由来する生物種: Bison bison (American bison)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 40758.09

構造登録者

Esposito, L.,Vitagliano, L.,Ruggiero, A.,Picone, D.,Leone, S.,Donnarumma, F. (登録日: 2019-02-07, 公開日: 2019-05-08, 最終更新日: 2024-10-16)

主引用文献

Esposito, L.,Donnarumma, F.,Ruggiero, A.,Leone, S.,Vitagliano, L.,Picone, D.
Structure, stability and aggregation propensity of a Ribonuclease A-Onconase chimera.
Int.J.Biol.Macromol., 133:1125-1133, 2019

PubMed Abstract: Structural roles of loop regions are frequently overlooked in proteins. Nevertheless, they may be key players in the definition of protein topology and in the self-assembly processes occurring through domain swapping. We here investigate the effects on structure and stability of replacing the loop connecting the last two β-strands of RNase A with the corresponding region of the more thermostable Onconase. The crystal structure of this chimeric variant (RNaseA-ONC) shows that its terminal loop size better adheres to the topological rules for the design of stabilized proteins, proposed by Baker and coworkers [43]. Indeed, RNaseA-ONC displays a thermal stability close to that of RNase A, despite the lack of Pro at position 114, which, due to its propensity to favor a cis peptide bond, has been identified as an important stabilizing factor of the native protein. Accordingly, RNaseA-ONC is significantly more stable than RNase A variants lacking Pro114; RNaseA-ONC also displays a higher propensity to form oligomers in native conditions when compared to either RNase A or Onconase. This finding demonstrates that modifications of terminal loops should to be carefully controlled in terms of size and sequence to avoid unwanted and/or potentially harmful aggregation processes.

PubMed: 31026530
DOI: 10.1016/j.ijbiomac.2019.04.164

実験手法

X-RAY DIFFRACTION (2.31 Å)