6UTE

Crystal structure of Z032 Fab in complex with WNV EDIII

6UTE の概要

• エントリーDOI: 10.2210/pdb6ute/pdb
• 分子名称: Z032 Fab heavy chain, Z032 Fab light chain, Envelope domain III, ... (4 entities in total)
• 機能のキーワード: viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 253678.76

構造登録者

Esswein, S.R.,Gristick, H.B.,Keeffe, J.R.,Bjorkman, P.J. (登録日: 2019-10-29, 公開日: 2020-04-15, 最終更新日: 2024-10-16)

主引用文献

Esswein, S.R.,Gristick, H.B.,Jurado, A.,Peace, A.,Keeffe, J.R.,Lee, Y.E.,Voll, A.V.,Saeed, M.,Nussenzweig, M.C.,Rice, C.M.,Robbiani, D.F.,MacDonald, M.R.,Bjorkman, P.J.
Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody.
Proc.Natl.Acad.Sci.USA, 117:9865-9875, 2020

PubMed Abstract: Recent epidemics demonstrate the global threat of Zika virus (ZIKV), a flavivirus transmitted by mosquitoes. Although infection is usually asymptomatic or mild, newborns of infected mothers can display severe symptoms, including neurodevelopmental abnormalities and microcephaly. Given the large-scale spread, symptom severity, and lack of treatment or prophylaxis, a safe and effective ZIKV vaccine is urgently needed. However, vaccine design is complicated by concern that elicited antibodies (Abs) may cross-react with other flaviviruses that share a similar envelope protein, such as dengue virus, West Nile virus, and yellow fever virus. This cross-reactivity may worsen symptoms of a subsequent infection through Ab-dependent enhancement. To better understand the neutralizing Ab response and risk of Ab-dependent enhancement, further information on germline Ab binding to ZIKV and the maturation process that gives rise to potently neutralizing Abs is needed. Here we use binding and structural studies to compare mature and inferred-germline Ab binding to envelope protein domain III of ZIKV and other flaviviruses. We show that affinity maturation of the light-chain variable domain is important for strong binding of the recurrent VH3-23/VK1-5 neutralizing Abs to ZIKV envelope protein domain III, and identify interacting residues that contribute to weak, cross-reactive binding to West Nile virus. These findings provide insight into the affinity maturation process and potential cross-reactivity of VH3-23/VK1-5 neutralizing Abs, informing precautions for protein-based vaccines designed to elicit germline versions of neutralizing Abs.

PubMed: 32321830
DOI: 10.1073/pnas.1919269117

実験手法

X-RAY DIFFRACTION (2.9 Å)