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結構生物學期末報告. 生技所 蕭孟昌 學號 M93360039. Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Science March 1998 VOL 392 P42-48 Lin Chen*, J. N. Mark Glover* † , Patrick G. Hogan ‡ , Anjana Rao ‡ & Stephen C. Harrison* †
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結構生物學期末報告 生技所 蕭孟昌 學號 M93360039
Structure of the DNA-bindingdomains from NFAT, Fos andJun bound specifically to DNA • Science March 1998 VOL 392 P42-48 • Lin Chen*, J. N. Mark Glover*†, Patrick G. Hogan‡, Anjana Rao‡ & Stephen C. Harrison*† • * Department of Molecular and Cellular Biology and †Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA‡Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA • PDB ID :1A02
WHAT QUESTION IS THIS PAPER WANT TO SOLVE • The interaction between NFAT (nuclear factor of activated T cells) and AP-1(Fos-Jun). • Explain the mechanism of combinatorial regulation of transcription.
WHAT WE CAN DO IN THIS STUDY • What amino acid sequences are conserved and what are these sequences function? • What DNA sequences are conserved and what are these sequences function? • Try to find out other TF has similar mechanism to NFAT and AP-1.
CONSERVED REGION OF NFAT • TRP399. • SER429(與DNA之間有INTERANTION) • ASN451. • THR604(與DNA之間有INTERANTION) • PRO643(與AP-1之間有INTERACTION) • PRO677(與AP-1之間有INTERACTION)
CONSERVED REGION OF AP-1 • ALA150(與DNA之間有INTERACTION) • ARG159(與NFAT之間有INTERACTION) • GLU160 (與NFAT之間有INTERACTION) • SER279(與NFAT和DNA之間都有INTERACTION) • VAL294(Jun and Fos 的交錯點)
ANALYSIS OF DNA SEQUENCE • DNA fragment that has the sequence of the distal antigen-receptor response element (ARRE2) from the murine IL-2 promoter23.
分析結果 • DNA sequence conserved region 生物上的功能性雖不若protein sequence 的顯著,但很明顯的和轉錄因子結合的DNA sequence仍具有高度的保留性。
AP FAMILY • 命運法則 • 調控基因的能力是否相同?