Crystallographic Study Of Zinc Finger Transcription Factors GATA4

The expression of GATA4 throughout the embryo and cardiac development is involved in the regulation of the development of normal cardiac morphology.According to the HGMD,123 mutations in GATA4 are involved in a variety of CHD cases,such as ToF,ASD,VSD and AVSD.Among them,AVSD patients accounted for all adult congenital heart disease patients 30% to 40%.GATA4 can regulate heart-specific transcription with other cardiac transcription factors such as Nkx2.5,T-box,GATA6,MEF2 C.In addition,GATA4 connects autophagy and the DDR to senescence and inflammation through TRAF3IP2 and IL1 A activation of NF-?B.GATA4 belongs to the DNA-binding protein family.The human GATA4 protein consists of 442 amino acids.GATA4 contains two unique zinc finger domains that form a DNA binding domain with adjacent highly conserved alkaline regions,a highly conserved zinc finger domain targeting nucleotide sequence element(A/T)GATA(A/G).So far,the exact mechanism for the interaction of GATA4 with DNA has not been clarified.The main contents of this thesis are as follows:(1)The GATA4 nucleic acid binding region protein was used as the study object,the target protein was purified by expression in the prokaryotic expression system.The GATA4 nucleic acid binding region protein and dsDNA complex were screened and the res?Lts show that the crystal structure with a resolution of 2.6 ? is collected by X-ray crystal diffraction.(2)Based on the function of GATA4 N-terminal protein,it was constructed and a series of clones were constructed.The purified GATA4 N-terminal protein was purified and crystallization.GATA4 and DNA,and laid a theoretical foundation for the subsequent study of the relationship between GATA4 and CHD embryonic development.Although the ideal GATA4 N-terminal protein crystals were not obtained,they laid the foundation for further studies on crystallography.