結構生物學期末報告 生技所 蕭孟昌 學號 M

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* †  * 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.

ANALYSIS OF NFAT

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)

ANALYSIS OF AP-1

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？

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