Molecular modeling on HIF-2α–ARNT dimer destabilization caused by R171A and/or V192D mutations in HIF-2α

摘要

Graphical abstract(A) F169D and H194A barely alter the structure, and therefore act as WT proteins.(B) V192D brings PAS-A and PAS-B domains closer and shrinks the opening to accommodate the ARNT PAS-A domain.(C) For R171A and R171A/V192D, the replacement of R171 moves the PAS-A and PAS-B interface downward, widening the opening.Display OmittedHighlights?Computational insights into the unbinding behavior caused by R171A and/or V192D mutation.?R171A and R171A/V192D have wider separation of PAS-A and PAS-B domains.?V192D has narrower separation of PAS-A and PAS-B domains.?HIF-2α carrying F169D or H194A maintains the similar separation as in wild-type so it can still bind with ARNT.?