Estradiol induces Allosteric Coupling and Partitioning of Sex Hormone Binding Globulin Monomers Among Conformational States
作者： Ravi Jasuja , Brian Lawney , Bhyravabhotla Jayaram , Liming Peng , Kelly M Thayer
DOI: 10.1016/J.ISCI.2021.102414
关键词:
摘要: Abstract Sex hormone-binding globulin (SHBG) regulates the transport and bioavailability of estradiol. The dynamics estradiol's binding to SHBG are incompletely understood although it is believed that estradiol binds each monomer dimer with identical affinity (Kd ∼2 nM). Contrary prevalent view, we show estradiol’s nonlinear "apparent" Kd changes varying concentrations. Estradiol’s influences residues in ligand pocket both monomers, differentially alters conformational energy landscapes monomers. Monomers not energetically or conformationally equivalent even fully-bound state. Conclusion: involves bidirectional, inter-monomeric allostery distribution monomers among various states. Inter-monomeric offers a mechanism extend range regulate hormone as concentrations vary widely during life.
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