7U2T

Influenza Neuraminidase N1-MI15-sNAp-174

7U2T の概要

• エントリーDOI: 10.2210/pdb7u2t/pdb
• EMDBエントリー: 26318 26319
• 分子名称: Influenza N1-MI15-sNAp-174, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: influenza, antigen, engineered protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• 由来する生物種: Influenza A virus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 172080.63

構造登録者

Acton, O.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2022-02-24, 公開日: 2022-04-20, 最終更新日: 2024-10-23)

主引用文献

Ellis, D.,Lederhofer, J.,Acton, O.J.,Tsybovsky, Y.,Kephart, S.,Yap, C.,Gillespie, R.A.,Creanga, A.,Olshefsky, A.,Stephens, T.,Pettie, D.,Murphy, M.,Sydeman, C.,Ahlrichs, M.,Chan, S.,Borst, A.J.,Park, Y.J.,Lee, K.K.,Graham, B.S.,Veesler, D.,King, N.P.,Kanekiyo, M.
Structure-based design of stabilized recombinant influenza neuraminidase tetramers.
Nat Commun, 13:1825-1825, 2022

PubMed Abstract: Influenza virus neuraminidase (NA) is a major antiviral drug target and has recently reemerged as a key target of antibody-mediated protective immunity. Here we show that recombinant NAs across non-bat subtypes adopt various tetrameric conformations, including an "open" state that may help explain poorly understood variations in NA stability across viral strains and subtypes. We use homology-directed protein design to uncover the structural principles underlying these distinct tetrameric conformations and stabilize multiple recombinant NAs in the "closed" state, yielding two near-atomic resolution structures of NA by cryo-EM. In addition to enhancing thermal stability, conformational stabilization improves affinity to protective antibodies elicited by viral infection, including antibodies targeting a quaternary epitope and the broadly conserved catalytic site. Stabilized NAs can also be integrated into viruses without affecting fitness. Our findings provide a deeper understanding of NA structure, stability, and antigenicity, and establish design strategies for reinforcing the conformational integrity of recombinant NA proteins.

PubMed: 35383176
DOI: 10.1038/s41467-022-29416-z

実験手法

ELECTRON MICROSCOPY (3.25 Å)