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

Add time:08/25/2019    Source:sciencedirect.com

Oxygen homeostasis in normal and tumor cells is mediated by hypoxia-inducible factors (HIFs), which are active as heterodimer complexes, such as HIF-2α–aryl hydrocarbon receptor nuclear translocator (ARNT) and HIF-1α–ARNT. A series of mutations on the interfaces between HIF-2α and ARNT and on the domain–domain interface within HIF-2α has been reported to exert varying effects on HIF-2α–ARNT dimerization. In the present study, molecular dynamic simulations were conducted to evaluate HIF-2α mutations, namely R171A, V192D, and R171A/V192D, which are not involved in the interaction with ARNT but impede HIF-2α–ARNT dimerization. Our results indicate that these mutations induct local conformation leading to a shortened (by V192D) or widened (by R171A and R171A/V192D) Y91–E346 separation distance, where E346 and Y91 are located on the HIF-2α and interact with ARNT according to electrostatic and geometrical shape complementarity, respectively.

We also recommend Trading Suppliers and Manufacturers of Arnt protein (cas 138391-32-9). Pls Click Website Link as below: cas 138391-32-9 suppliers

Prev:The aryl hydrocarbon receptor nuclear translocator-interacting protein 2 suppresses the estrogen receptor signaling via an Arnt-dependent mechanism
Next:Purification and characterization of the l-Ara4N transferase protein ArnT from Salmonella typhimurium)