5KEL

EBOV GP in complex with variable Fab domains of IgGs c2G4 and c13C6

5KEL の概要

• エントリーDOI: 10.2210/pdb5kel/pdb
• 関連するPDBエントリー: 5KEM 5KEN
• EMDBエントリー: 8240 8241 8242
• 分子名称: Ebola surface glycoprotein, GP1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: ebola virus surface glycoprotein, therapeutic antibody cocktail, zmapp, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Zaire ebolavirus (strain Mayinga-76) (ZEBOV); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 359998.05

構造登録者

Pallesen, J.,Murin, C.D.,de Val, N.,Cottrell, C.A.,Hastie, K.M.,Turner, H.L.,Fusco, M.L.,Flyak, A.I.,Zeitlin, L.,Crowe Jr., J.E.,Andersen, K.G.,Saphire, E.O.,Ward, A.B. (登録日: 2016-06-09, 公開日: 2016-09-07, 最終更新日: 2024-10-30)

主引用文献

Pallesen, J.,Murin, C.D.,de Val, N.,Cottrell, C.A.,Hastie, K.M.,Turner, H.L.,Fusco, M.L.,Flyak, A.I.,Zeitlin, L.,Crowe, J.E.,Andersen, K.G.,Saphire, E.O.,Ward, A.B.
Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.
Nat Microbiol, 1:16128-16128, 2016

PubMed Abstract: The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

PubMed: 27562261
DOI: 10.1038/nmicrobiol.2016.128

実験手法

ELECTRON MICROSCOPY (4.3 Å)