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 (K(a)=4.0x10(7) M(-1) versus 8.6x10(8) 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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