The Interaction Between Orphan Nuclear Receptor Nur77 And Co-activator SRC2

Nuclear receptors(NR)are a class of evolutionarily related transcription factors with similar structural characteristics.By binding physiological ligands and various co-regulatory factors,the classical nuclear receptors can play a variety of roles to participate in many physiological activities in the cell,such as proliferation,apoptosis,differentiation,autophagy,among others.Besides classical nuclear receptors,there is a group of nuclear receptor whose endogenous ligands have not been identified up to date.These so-called orphan nuclear receptors can regulate transcription with the help of co-regulatory factors.It is known that there is an AF-1 site where the co-activators bind in the N-terminal portion of the nuclear receptors.There is also an AF-2 site in the C-terminal portion of the nuclear receptor for binding the co-activators.The location and sequence of many AF-2 sites are investigated for many classical nuclear receptors,but the AF-2 site for the orphan nuclear receptors is still to be elucidated.Nur77,a member of the NR4A family,is also an orphan nuclear receptors.Its transcription activity requires the binding of co-regulatory factors like SRC2(p160 Steroid Receptor Co-activator 2).In this thesis,we determined the complex structure of the Nur77 LBD and a SRC2 peptide.In conjunction with other experiments,a possible binding site for Nur77 interaction with SRC2 was determined.