Fig. 5. Antibody binding causes allosteric conformational changes in the GD and FT.

a, Comparison between the [¹⁵N,¹H]-TROSY spectra of free rmPrP_90–231 versus that bound to the ^hcY104A pomolog. Chemical-shift differences, reflecting subtle alterations of the local chemical structure, were visible not only in the epitope but also at distant sites in the GD and FT. Residues affected by antibody binding are in color on PrP^C (GD and part of the FT are shown on a MD model of PrP). Differences between toxic and protective antibodies are evident in the α2–α3 loop (the Y104A complex is identical to free PrP^C) and in the FT region closer to the GD. b, Content of secondary structure estimated from CD spectra of the rmPrP–pomologs complexes. ‘Calculated’ indicates the secondary structure content if the rmPrP and pomolog did not change upon binding. POM1 displayed increased content of irregular structure (measured versus calculated) when in complex with full rmPrP_23–231, but identical content when in complex with a construct lacking the FT (rmPrP_90–231). This indicates that the FT changes conformation upon POM1 binding. Conversely, no differences were detected with the protective pomolog ^hcY104A.