9EIT

NCS.1 Fab in complex with N5 NA of A/shorebird/Delaware Bay/309/2016 (DB16, H10N5) -- 4 Fabs

9EIT の概要

• エントリーDOI: 10.2210/pdb9eit/pdb
• EMDBエントリー: 48093
• 分子名称: NCS.1 Heavy Chain, NCS.1 Light Chain, Neuraminidase, ... (6 entities in total)
• 機能のキーワード: neuraminidase, ncs.1, tetramer, antibody, fab, n5, h10n5, db6, viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 276048.98

構造登録者

Borst, A.J. (登録日: 2024-11-26, 公開日: 2025-08-13)

主引用文献

Lederhofer, J.,Borst, A.J.,Nguyen, L.,Gillespie, R.A.,Williams, C.J.,Walker, E.L.,Raab, J.E.,Yap, C.,Ellis, D.,Creanga, A.,Tan, H.X.,Do, T.H.T.,Ravichandran, M.,McDermott, A.B.,Le Sage, V.,Andrews, S.F.,Graham, B.S.,Wheatley, A.K.,Reed, D.S.,King, N.P.,Kanekiyo, M.
Structural convergence and water-mediated substrate mimicry enable broad neuraminidase inhibition by human antibodies.
Nat Commun, 16:7068-7068, 2025

PubMed Abstract: Influenza has been responsible for multiple global pandemics and seasonal epidemics and claimed millions of lives. The imminent threat of a panzootic outbreak of avian influenza H5N1 virus underscores the urgent need for pandemic preparedness and effective countermeasures, including monoclonal antibodies (mAbs). Here, we characterize human mAbs that target the highly conserved catalytic site of viral neuraminidase (NA), termed NCS mAbs, and the molecular basis of their broad specificity. Cross-reactive NA-specific B cells were isolated by using stabilized NA probes of non-circulating subtypes. We found that NCS mAbs recognized multiple NAs of influenza A as well as influenza B NAs and conferred prophylactic protections in mice against H1N1, H5N1, and influenza B viruses. Cryo-electron microscopy structures of two NCS mAbs revealed that they rely on structural mimicry of sialic acid, the substrate of NA, by coordinating not only amino acid side chains but also water molecules, enabling inhibition of NA activity across multiple influenza A and B viruses, including avian influenza clade 2.3.4.4b H5N1 viruses. Our results provide a molecular basis for the broad reactivity and inhibitory activity of NCS mAbs targeting the catalytic site of NA through substrate mimicry.

PubMed: 40750617
DOI: 10.1038/s41467-025-62339-z

実験手法

ELECTRON MICROSCOPY (3.35 Å)