1. Partially structured state of the functional VH domain of the mouse anti-ferritin antibody F11
- Author
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Sergey P. Martsev, Anatoly P. Dubnovitsky, Sergey M. Deyev, Oleg A Stremovsky, Alexander A. Chumanevich, Zinaida I. Kravchuk, and Yaroslav I Tsybovsky
- Subjects
Protein Folding ,Protein Conformation ,medicine.drug_class ,Immunoglobulin gamma-Chains ,Antibody Affinity ,Immunoglobulin Variable Region ,Biophysics ,Antibody combining site ,VH domain ,Monoclonal antibody ,Immunoglobulin light chain ,Biochemistry ,Mice ,Structural Biology ,Genetics ,medicine ,Animals ,Molecular Biology ,Calorimetry, Differential Scanning ,biology ,Chemistry ,Circular Dichroism ,Antibodies, Monoclonal ,Antigen-binding ,Cell Biology ,State (functional analysis) ,Antigen binding ,Molecular biology ,Ferritin ,Spectrometry, Fluorescence ,Ferritins ,Domain (ring theory) ,biology.protein ,Antibody folding and stability ,Antibody - Abstract
An antibody combining site generally involves the two variable domains, VH from the heavy and VL from the light chain. We expressed the individual VH domain of the mouse anti-human ferritin monoclonal antibody F11. The loss of affinity was not dramatic (Ka=4.0×107 M−1 versus 8.6×108 M−1 for the parent antibody) and comparable to that previously observed for other VHs. However, the functional VH domain adopted a partially structured state with a significant amount of distorted secondary and compact yet greatly destabilized tertiary structures, as demonstrated by spectroscopic and calorimetric probes. These data provide the first description for a functional antibody domain that meets all the criteria of a partially structured state.
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