National Institutes of Health/Office of the Director
S10RR031780
米国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2021 タイトル: High-resolution asymmetric structure of a Fab-virus complex reveals overlap with the receptor binding site. 著者: Daniel J Goetschius / Samantha R Hartmann / Lindsey J Organtini / Heather Callaway / Kai Huang / Carol M Bator / Robert E Ashley / Alexander M Makhov / James F Conway / Colin R Parrish / Susan L Hafenstein / 要旨: Canine parvovirus is an important pathogen causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Overlap on the surface of parvovirus capsids ...Canine parvovirus is an important pathogen causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Overlap on the surface of parvovirus capsids between the antigenic epitope and the receptor binding site has contributed to cross-species transmission, giving rise to closely related variants. It has been shown that Mab 14 strongly binds and neutralizes canine but not feline parvovirus, suggesting this antigenic site also controls species-specific receptor binding. To visualize the conformational epitope at high resolution, we solved the cryogenic electron microscopy (cryo-EM) structure of the Fab-virus complex. We also created custom software, Icosahedral Subparticle Extraction and Correlated Classification, to solve a Fab-virus complex with only a few Fab bound per capsid and visualize local structures of the Fab-bound and -unbound antigenic sites extracted from the same complex map. Our results identified the antigenic epitope that had significant overlap with the receptor binding site, and the structures revealed that binding of Fab induced conformational changes to the virus. We were also able to assign the order and position of attached Fabs to allow assessment of complementarity between the Fabs bound to different positions. This approach therefore provides a method for using cryo-EM to investigate complementarity of antibody binding.
履歴
登録
2021年3月18日
登録サイト: RCSB / 処理サイト: RCSB
改定 1.0
2021年7月28日
Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: EM metadata / Data content type: EM metadata / Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / タイプ: Initial release
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Data content type: Image / Data content type: Image / Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: Primary map / Data content type: Primary map / Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: Image / Data content type: Image / Provider: repository / タイプ: Initial release
改定 1.0
2021年7月28日
Data content type: Primary map / Data content type: Primary map / Provider: repository / タイプ: Initial release
改定 1.0
2021年7月28日
Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / タイプ: Initial release
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2021年7月28日
Data content type: Image / Data content type: Image / Provider: repository / タイプ: Initial release
改定 1.0
2021年7月28日
Data content type: Primary map / Data content type: Primary map / Provider: repository / タイプ: Initial release
Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / カテゴリ: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name
電子線照射量: 60 e/Å2 フィルム・検出器のモデル: FEI FALCON III (4k x 4k)
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解析
ソフトウェア
名称: PHENIX / バージョン: 1.17.1-3660_3260: / 分類: 精密化
EMソフトウェア
名称: PHENIX / カテゴリ: モデル精密化
CTF補正
タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION
3次元再構成
解像度: 2.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 162627 詳細: Asymmetric reconstruction, particle number is 162,627*10.2 orientations per particle 対称性のタイプ: POINT