6EK2

CRYSTAL STRUCTURE OF HUMAN CD81 LARGE EXTRACELLULAR LOOP IN COMPLEX WITH SINGLE CHAIN FV FRAGMENT 10

6EK2 の概要

• エントリーDOI: 10.2210/pdb6ek2/pdb
• 関連するPDBエントリー: 5DFW 6EJG 6EJM
• 分子名称: CD81 antigen, SINGLE CHAIN FV FRAGMENT (3 entities in total)
• 機能のキーワード: helical bundle, antibody-antigen complex, cell adhesion
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 74350.33

構造登録者

Harris, S.F.,Villasenor, A.,Kuglstatter, A. (登録日: 2017-09-25, 公開日: 2018-05-30, 最終更新日: 2024-10-23)

主引用文献

Nelson, B.,Adams, J.,Kuglstatter, A.,Li, Z.,Harris, S.F.,Liu, Y.,Bohini, S.,Ma, H.,Klumpp, K.,Gao, J.,Sidhu, S.S.
Structure-Guided Combinatorial Engineering Facilitates Affinity and Specificity Optimization of Anti-CD81 Antibodies.
J. Mol. Biol., 430:2139-2152, 2018

PubMed Abstract: Hepatitis C viral infection is the major cause of chronic hepatitis that affects as many as 71 million people worldwide. Rather than target the rapidly shifting viruses and their numerous serotypes, four independent antibodies were made to target the host antigen CD81 and were shown to block hepatitis C viral entry. The single-chain variable fragment of each antibody was crystallized in complex with the CD81 large extracellular loop in order to guide affinity maturation of two distinct antibodies by phage display. Affinity maturation of antibodies using phage display has proven to be critical to therapeutic antibody development and typically involves modification of the paratope for increased affinity, improved specificity, enhanced stability or a combination of these traits. One antibody was engineered for increased affinity for human CD81 large extracellular loop that equated to increased efficacy, while the second antibody was engineered for cross-reactivity with cynomolgus CD81 to facilitate animal model testing. The use of structures to guide affinity maturation library design demonstrates the utility of combining structural analysis with phage display technologies.

PubMed: 29778602
DOI: 10.1016/j.jmb.2018.05.018

実験手法

X-RAY DIFFRACTION (2.65 Å)