AIM-A1 and type 2B mutants reveals conformational differences. (A-G) Volcano plots showing differences in deuterium uptake among shared peptides after 10 seconds of exchange. The threshold for significance (data points above the dotted lines) requires both statistical significance of P ≤ .01 and a minimum difference of 0.5 dalton per peptide. Plots were generated using HD-eXplosion version 1.2. Peptides with significant HDX differences are displayed in color in the quadrant of the AIM-A1 variant with greater deuterium uptake. (H) Relative deuterium uptake over time for a representative peptide in the α3β4 loop. All type 2B VWD mutations tested have increased solvent accessibility in this region compared with WT. (I) Representative uptake of peptide in β3α2 loop showing P1266L has protection comparable with WT in this region at the fastest time point tested but loses this protection over time similarly to other type 2B VWD mutants. The crystal structure of AIM-A1 (PDB:7A6O) in gray and the indicated peptide mapped in black are displayed on each graph.

AIM-A1 and type 2B mutants reveals conformational differences. (A-G) Volcano plots showing differences in deuterium uptake among shared peptides after 10 seconds of exchange. The threshold for significance (data points above the dotted lines) requires both statistical significance of P ≤ .01 and a minimum difference of 0.5 dalton per peptide. Plots were generated using HD-eXplosion version 1.2. Peptides with significant HDX differences are displayed in color in the quadrant of the AIM-A1 variant with greater deuterium uptake. (H) Relative deuterium uptake over time for a representative peptide in the α3β4 loop. All type 2B VWD mutations tested have increased solvent accessibility in this region compared with WT. (I) Representative uptake of peptide in β3α2 loop showing P1266L has protection comparable with WT in this region at the fastest time point tested but loses this protection over time similarly to other type 2B VWD mutants. The crystal structure of AIM-A1 (PDB:7A6O) in gray and the indicated peptide mapped in black are displayed on each graph.

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