1A14

COMPLEX BETWEEN NC10 ANTI-INFLUENZA VIRUS NEURAMINIDASE SINGLE CHAIN ANTIBODY WITH A 5 RESIDUE LINKER AND INFLUENZA VIRUS NEURAMINIDASE

1A14 の概要

• エントリーDOI: 10.2210/pdb1a14/pdb
• 分子名称: NEURAMINIDASE, NC10 FV (HEAVY CHAIN), NC10 FV (LIGHT CHAIN), ... (7 entities in total)
• 機能のキーワード: complex (antibody-antigen), single-chain antibody, glycosylated protein, complex (antibody-antigen) complex, complex (antibody/antigen)
• 由来する生物種: Mus musculus (house mouse); 詳細
• 細胞内の位置: Virion membrane (By similarity): P03472
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 70069.18

構造登録者

Malby, R.L.,Mccoy, A.J.,Kortt, A.A.,Hudson, P.J.,Colman, P.M. (登録日: 1997-12-21, 公開日: 1998-05-13, 最終更新日: 2024-11-06)

主引用文献

Malby, R.L.,McCoy, A.J.,Kortt, A.A.,Hudson, P.J.,Colman, P.M.
Three-dimensional structures of single-chain Fv-neuraminidase complexes.
J.Mol.Biol., 279:901-910, 1998

PubMed Abstract: The structure of the complex between a recombinant single-chain Fv construct of antibody NC10 with a five-residue peptide linker between VH and VL (termed scFv(5)), and its antigen, tetrameric neuraminidase from influenza virus (NA), has been determined and refined at 2.5 A resolution. The antibody-antigen binding interface is very similar to that of a similar NC10 scFv-NA complex in which the scFv has a 15-residue peptide linker (scFv(15)), and the NC10 Fab-NA complex. However, scFv(5) and scFv(15) have different stoichiometries in solution. While scFv(15) is predominantly monomeric in solution, scFv(5) forms dimers exclusively, because the five-residue linker is not long enough to permit VH and VL domains from the same polypeptide associating and forming an antigen-binding site. Upon forming a complex with NA, scFv(15) forms a approximately 300 kDa complex corresponding to one NA tetramer binding four scFv(15) monomers, while scFv(5) forms a approximately 590 kDa complex, corresponding to two NA tetramers crosslinked by four bivalent scFv(5) dimers. However, the dimeric scFv(5) in the scFv(5)-NA crystals does not crosslink NA tetramers, and modelling studies indicate that it is not possible to pack four dimeric and simultaneously bivalent scFvs between the NA tetramers with only a five-residue linker between VH and VL. The inability arises from the exacting requirement to orient the two antigen-binding surfaces to bind the tetrameric NA antigen while avoiding steric clashes with NC10 scFv(5) dimers bound to other sites on the NA tetramer. The utility of bivalent or bifunctional scFvs with short linkers may therefore be restricted by the steric constraints imposed by binding multivalent antigens.

PubMed: 9642070
DOI: 10.1006/jmbi.1998.1794

実験手法

X-RAY DIFFRACTION (2.5 Å)