1IC4

CRYSTAL STRUCTURE OF HYHEL-10 FV MUTANT(HD32A)-HEN LYSOZYME COMPLEX

Summary for 1IC4

• Entry DOI: 10.2210/pdb1ic4/pdb
• Related: 1ic5 1ic7
• Descriptor: LYSOZYME BINDING IG KAPPA CHAIN, IGG1 FAB CHAIN H, LYSOZYME C, ... (4 entities in total)
• Functional Keywords: antigen-antibody complex, hyhel-10, anti-hen egg white lysozyme antibody, protein binding-hydrolase complex, protein binding/hydrolase
• Biological source: Mus musculus (house mouse); More
• Cellular location: Secreted: P00698
• Total number of polymer chains: 3
• Total formula weight: 38706.90

Authors

Shiroishi, M.,Yokota, A.,Tsumoto, K.,Kondo, H.,Nishimiya, Y.,Horii, K.,Matsushima, M.,Ogasahara, K.,Yutani, K.,Kumagai, I. (deposition date: 2001-03-30, release date: 2001-07-18, Last modification date: 2024-10-30)

Primary citation

Shiroishi, M.,Yokota, A.,Tsumoto, K.,Kondo, H.,Nishimiya, Y.,Horii, K.,Matsushima, M.,Ogasahara, K.,Yutani, K.,Kumagai, I.
Structural evidence for entropic contribution of salt bridge formation to a protein antigen-antibody interaction: the case of hen lysozyme-HyHEL-10 Fv complex.
J.Biol.Chem., 276:23042-23050, 2001

PubMed 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.

PubMed: 11297547
DOI: 10.1074/jbc.M100480200

Experimental method

X-RAY DIFFRACTION (2.5 Å)