Crystal structure of anti-hen egg white lysozyme antibody (HyHEL-10) Fv- antigen complex. Local structural changes in the protein antigen and water- mediated interactions of Fv-antigen and light chain-heavy chain interfaces

Hidemasa Kondo, Mitsunori Shiroishi, Masaaki Matsushima, Kouhei Tsumoto, Izumi Kumagai

研究成果: ジャーナルへの寄稿記事

62 引用 (Scopus)

抄録

In order to address the recognition mechanism of the fragments of antibody variable regions, termed Fv, toward their target antigen, an x-ray crystal structure of an anti-hen egg white lysozyme antibody (HyHEL-10) Fv fragment complexed with its cognate antigen, hen egg white lysozyme (HEL), was solved at 2.3 Å. The overall structure of the complex is similar to that reported in a previous article dealing with the Fab fragment-HEL complex (PDB ID code, 3HFM). However, the areas of Fv covered by HEL upon complex formation increased by about 100 Å2 in comparison with the Fab-HEL complex, and two local structural differences were observed in the heavy chain of the variable region (VH). In addition, small but significant local structural changes were observed in the antigen, HEL. The x-ray data permitted the identification of two water molecules between the VH and HEL and six water molecules retained in the interface between the antigen and the light chain complementarity determining regions (CDRs) 2 and 3 (CDR-L2 and CDR-L3). These water molecules bridge the antigen-antibody interface through hydrogen bond formation in the VL-HEL interface. Eleven water molecules were found to complete the imperfect VH-VL interface, suggesting that solvent molecules mediate the stabilization of interaction between variable regions. These results suggest that the unfavorable effect of deletion of constant regions on the antigen-antibody interaction is compensated by an increase in favorable interactions, including structural changes in the antigen-antibody interface and solvent-mediated hydrogen bond formation upon complex formation, which may lead to a minimum decreased affinity of the antibody Fv fragment toward its antigen.

元の言語英語
ページ(範囲)27623-27631
ページ数9
ジャーナルJournal of Biological Chemistry
274
発行部数39
DOI
出版物ステータス出版済み - 9 24 1999

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Egg White
Muramidase
Crystal structure
Complementarity Determining Regions
Light
Antigens
Water
Antibodies
Proteins
Molecules
Immunoglobulin Variable Region
Hydrogen
Hydrogen bonds
X-Rays
X rays
Immunoglobulin Fragments
Immunoglobulin Fab Fragments
hen egg lysozyme
Stabilization

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Crystal structure of anti-hen egg white lysozyme antibody (HyHEL-10) Fv- antigen complex. Local structural changes in the protein antigen and water- mediated interactions of Fv-antigen and light chain-heavy chain interfaces. / Kondo, Hidemasa; Shiroishi, Mitsunori; Matsushima, Masaaki; Tsumoto, Kouhei; Kumagai, Izumi.

:: Journal of Biological Chemistry, 巻 274, 番号 39, 24.09.1999, p. 27623-27631.

研究成果: ジャーナルへの寄稿記事

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title = "Crystal structure of anti-hen egg white lysozyme antibody (HyHEL-10) Fv- antigen complex. Local structural changes in the protein antigen and water- mediated interactions of Fv-antigen and light chain-heavy chain interfaces",
abstract = "In order to address the recognition mechanism of the fragments of antibody variable regions, termed Fv, toward their target antigen, an x-ray crystal structure of an anti-hen egg white lysozyme antibody (HyHEL-10) Fv fragment complexed with its cognate antigen, hen egg white lysozyme (HEL), was solved at 2.3 {\AA}. The overall structure of the complex is similar to that reported in a previous article dealing with the Fab fragment-HEL complex (PDB ID code, 3HFM). However, the areas of Fv covered by HEL upon complex formation increased by about 100 {\AA}2 in comparison with the Fab-HEL complex, and two local structural differences were observed in the heavy chain of the variable region (VH). In addition, small but significant local structural changes were observed in the antigen, HEL. The x-ray data permitted the identification of two water molecules between the VH and HEL and six water molecules retained in the interface between the antigen and the light chain complementarity determining regions (CDRs) 2 and 3 (CDR-L2 and CDR-L3). These water molecules bridge the antigen-antibody interface through hydrogen bond formation in the VL-HEL interface. Eleven water molecules were found to complete the imperfect VH-VL interface, suggesting that solvent molecules mediate the stabilization of interaction between variable regions. These results suggest that the unfavorable effect of deletion of constant regions on the antigen-antibody interaction is compensated by an increase in favorable interactions, including structural changes in the antigen-antibody interface and solvent-mediated hydrogen bond formation upon complex formation, which may lead to a minimum decreased affinity of the antibody Fv fragment toward its antigen.",
author = "Hidemasa Kondo and Mitsunori Shiroishi and Masaaki Matsushima and Kouhei Tsumoto and Izumi Kumagai",
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T1 - Crystal structure of anti-hen egg white lysozyme antibody (HyHEL-10) Fv- antigen complex. Local structural changes in the protein antigen and water- mediated interactions of Fv-antigen and light chain-heavy chain interfaces

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AU - Shiroishi, Mitsunori

AU - Matsushima, Masaaki

AU - Tsumoto, Kouhei

AU - Kumagai, Izumi

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