دورية أكاديمية
Three-dimensional structures of single-chain Fv-neuraminidase complexes.
| العنوان: | Three-dimensional structures of single-chain Fv-neuraminidase complexes. |
|---|---|
| المؤلفون: | Malby RL; Biomolecular Research Institute, 343 Royal Parade, Parkville, 3052, Australia., McCoy AJ, Kortt AA, Hudson PJ, Colman PM |
| المصدر: | Journal of molecular biology [J Mol Biol] 1998 Jun 19; Vol. 279 (4), pp. 901-10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print Cited Medium: Print ISSN: 0022-2836 (Print) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: 1959- : London : Academic Press |
| مواضيع طبية MeSH: | Protein Conformation*, Immunoglobulin Fragments/*chemistry , Neuraminidase/*chemistry, Animals ; Binding Sites ; Crystallography, X-Ray ; Immunoglobulin Fragments/metabolism ; Immunoglobulin Variable Region/chemistry ; Immunoglobulin Variable Region/metabolism ; Models, Molecular ; Neuraminidase/metabolism ; Protein Binding ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/metabolism |
| مستخلص: | 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. (Copyright 1998 Academic Press Limited.) |
| المشرفين على المادة: | 0 (Immunoglobulin Fragments) 0 (Immunoglobulin Variable Region) 0 (Recombinant Fusion Proteins) 0 (immunoglobulin Fv) EC 3.2.1.18 (Neuraminidase) |
| تواريخ الأحداث: | Date Created: 19980627 Date Completed: 19980721 Latest Revision: 20061115 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1006/jmbi.1998.1794 |
| PMID: | 9642070 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0022-2836 |
|---|---|
| DOI: | 10.1006/jmbi.1998.1794 |