6Y07

Designing a Granulopoietic Protein by Topological Rescaffolding 1: Sohair

6Y07 の概要

• エントリーDOI: 10.2210/pdb6y07/pdb
• NMR情報: BMRB: 34489
• 分子名称: sohair (1 entity in total)
• 機能のキーワード: protein design, receptor modulator, gcsf analog, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20297.09

構造登録者

ElGamacy, M.,Coles, M. (登録日: 2020-02-06, 公開日: 2020-03-18, 最終更新日: 2024-05-15)

主引用文献

Hernandez Alvarez, B.,Skokowa, J.,Coles, M.,Mir, P.,Nasri, M.,Maksymenko, K.,Weidmann, L.,Rogers, K.W.,Welte, K.,Lupas, A.N.,Muller, P.,ElGamacy, M.
Design of novel granulopoietic proteins by topological rescaffolding.
Plos Biol., 18:e3000919-e3000919, 2020

PubMed Abstract: Computational protein design is rapidly becoming more powerful, and improving the accuracy of computational methods would greatly streamline protein engineering by eliminating the need for empirical optimization in the laboratory. In this work, we set out to design novel granulopoietic agents using a rescaffolding strategy with the goal of achieving simpler and more stable proteins. All of the 4 experimentally tested designs were folded, monomeric, and stable, while the 2 determined structures agreed with the design models within less than 2.5 Å. Despite the lack of significant topological or sequence similarity to their natural granulopoietic counterpart, 2 designs bound to the granulocyte colony-stimulating factor (G-CSF) receptor and exhibited potent, but delayed, in vitro proliferative activity in a G-CSF-dependent cell line. Interestingly, the designs also induced proliferation and differentiation of primary human hematopoietic stem cells into mature granulocytes, highlighting the utility of our approach to develop highly active therapeutic leads purely based on computational design.

PubMed: 33351791
DOI: 10.1371/journal.pbio.3000919

実験手法

SOLUTION NMR