7OOI

Anti-EphA1 JD1 VH domain

7OOI の概要

• エントリーDOI: 10.2210/pdb7ooi/pdb
• 分子名称: JD1 VH domain, SULFATE ION (3 entities in total)
• 機能のキーワード: vh domain, epha1, immune system
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27814.67

構造登録者

Ereno-Orbea, J.,Nilvebrant, J.,Sidhu, S.,Julien, J.P. (登録日: 2021-05-27, 公開日: 2021-10-06, 最終更新日: 2024-10-23)

主引用文献

Nilvebrant, J.,Ereno-Orbea, J.,Gorelik, M.,Julian, M.C.,Tessier, P.M.,Julien, J.P.,Sidhu, S.S.
Systematic Engineering of Optimized Autonomous Heavy-Chain Variable Domains.
J.Mol.Biol., 433:167241-167241, 2021

PubMed Abstract: Autonomous heavy-chain variable (V) domains are the smallest functional antibody fragments, and they possess unique features, including small size and convex paratopes, which provide enhanced targeting of concave epitopes that are difficult to access with larger conventional antibodies. However, human V domains have evolved to fold and function with a light chain partner, and alone, they typically suffer from low stability and high aggregation propensity. Development of autonomous human V domains, in which aggregation propensity is reduced without compromising antigen recognition, has proven challenging. Here, we used an autonomous human V domain as a scaffold to construct phage-displayed synthetic libraries in which aspartate was systematically incorporated at different paratope positions. In selections, the library yielded many anti-EphA1 receptor V domains, which were characterized in detail. Structural analyses of a parental anti-EphA1 V domain and an improved variant provided insights into the effects of aspartate and other substitutions on preventing aggregation while retaining function. Our naïve libraries and in vitro selection procedures offer a systematic approach to generating highly functional autonomous human V domains that resist aggregation and could be used for basic research and biomedical applications.

PubMed: 34508727
DOI: 10.1016/j.jmb.2021.167241

実験手法

X-RAY DIFFRACTION (2.28 Å)