Conformational plasticity of RAS Q61 family of neoepitopes results in distinct features for targeted recognition.

ABSTRACT: The conformational landscapes of peptide/human leucocyte antigen (pHLA) protein complexes encompassing tumor neoantigens provide a rationale for target selection towards autologous T cell, vaccine, and antibody-based therapeutic modalities. Here, using complementary biophysical and computational methods, we characterize recurrent RAS_55-64 Q61 neoepitopes presented by the common HLA-A*01:01 allotype. We integrate sparse NMR restraints with Rosetta docking to determine the solution structure of NRAS^Q61K/HLA-A*01:01, which enables modeling of other common RAS_55-64 neoepitopes. Hydrogen/deuterium exchange mass spectrometry experiments alongside molecular dynamics simulations reveal differences in solvent accessibility and conformational plasticity across a pane

SUBMITTER: McShan AC 

PROVIDER: S-EPMC10713829 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature