Structural evidence for entropic contribution of salt bridge formation to a protein antigen-antibody interaction. The case of hen lysozyme-HyHEL-10 Fv complex

Mitsunori Shiroishi, Akiko Yokota, Kouhei Tsumoto, Hidemasa Kondo, Yoshiyuki Nishimiya, Katsunori Horii, Masaaki Matsushima, Kyoko Ogasahara, Katsuhide Yutani, Izumi Kumagai

Research output: Contribution to journalArticle

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Abstract

A structural and thermodynamic study of the entropic contribution of salt bridge formation to the interaction between hen egg white lysozyme (HEL) and the variable domain fragment (Fv) of anti-HEL antibody, HyHEL-10, was carried out. Three Fv mutants (HD32A, HD96A, and HD32AD96A) were prepared, and the interactions between the mutant Fvs and HEL were investigated. Crystallography revealed that the overall structures of these mutant complexes were almost identical to that of wild-type Fv. Little structural changes were observed in the HD32AD96A mutant-HEL complex, and two water molecules were introduced into the mutation site, indicating that the two water molecules structurally compensated for the complete removal of the salt bridges. This result suggests that the entropic contribution of the salt bridge originates from dehydration. In the singly mutated complexes, one water molecule was also introduced into the mutated site, bridging the antigen-antibody interface. However, a local structural difference was observed in the HD32A Fv-HEL complex, and conformational changes occurred due to changes in the relative orientation of the heavy chain to the light chain upon complexation in HD96A Fv-HEL complexes. The reduced affinity of these single mutants for the antigen originates from the increase in entropy loss, indicating that these structural changes also introduced an increase in entropy loss. These results suggest that salt bridge formation makes an entropic contribution to the protein antigen-antibody interaction through reduction of entropy loss due to dehydration and structural changes.

Original languageEnglish
Pages (from-to)23042-23050
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number25
DOIs
Publication statusPublished - Jun 22 2001

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Egg White
Muramidase
Salts
Antigens
Antibodies
Entropy
Proteins
Dehydration
Molecules
Water
Immunoglobulin Variable Region
Crystallography
Complexation
Thermodynamics
hen egg lysozyme
Light
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Structural evidence for entropic contribution of salt bridge formation to a protein antigen-antibody interaction. The case of hen lysozyme-HyHEL-10 Fv complex. / Shiroishi, Mitsunori; Yokota, Akiko; Tsumoto, Kouhei; Kondo, Hidemasa; Nishimiya, Yoshiyuki; Horii, Katsunori; Matsushima, Masaaki; Ogasahara, Kyoko; Yutani, Katsuhide; Kumagai, Izumi.

In: Journal of Biological Chemistry, Vol. 276, No. 25, 22.06.2001, p. 23042-23050.

Research output: Contribution to journalArticle

Shiroishi, M, Yokota, A, Tsumoto, K, Kondo, H, Nishimiya, Y, Horii, K, Matsushima, M, Ogasahara, K, Yutani, K & Kumagai, I 2001, 'Structural evidence for entropic contribution of salt bridge formation to a protein antigen-antibody interaction. The case of hen lysozyme-HyHEL-10 Fv complex', Journal of Biological Chemistry, vol. 276, no. 25, pp. 23042-23050. https://doi.org/10.1074/jbc.M100480200
Shiroishi, Mitsunori ; Yokota, Akiko ; Tsumoto, Kouhei ; Kondo, Hidemasa ; Nishimiya, Yoshiyuki ; Horii, Katsunori ; Matsushima, Masaaki ; Ogasahara, Kyoko ; Yutani, Katsuhide ; Kumagai, Izumi. / Structural evidence for entropic contribution of salt bridge formation to a protein antigen-antibody interaction. The case of hen lysozyme-HyHEL-10 Fv complex. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 25. pp. 23042-23050.
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