Murine norovirus (MNV) undergoes large conformational changes in response to the environment. The T=3 icosahedral capsid is composed of 180 copies of ~58 kDa VP1 that has N-terminal (N), shell (S) and C-terminal protruding (P) domains. In phosphate buffered saline, the P domains are loosely tethered to the shell and float ~15Å above the surface. At conditions found in the gut (i.e. low pH with high metal ion and bile salt concentrations) the P domain rotates and drops onto the shell with intra P domain changes that enhance receptor interactions while blocking antibody binding. Two of our monoclonal antibodies (2D3 and 4F9) have broad strain recognition and the only escape mutants, V339I and D348E, are located on the C D loop and ~20 Å from the epitope. Here we determined the cryo-EM structures of V339I and D348E at neutral pH +/- metal ions and bile salts. These allosteric escape mutants are constitutively in the activated state without the addition of metal ions or bile salts, thus explaining how they escape neutralization. Dynamic simulations of the P domain further suggest that movement of the C D loop may be the rate limiting step in the conformational change and that V339I increases the motion of the A B /E F loops compared to wt, making it easier for the virus to transition to the activated state. These findings have important implications for norovirus vaccine design since they uncover a form of the viral capsid that should lend superior immune protection against subsequent challenge by wild type virus.