dna binding domains and activation domains of transcription factors
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DNA binding domains and activation domains of transcription factors. A survey of DNA binding domains. Zn -containing domains 6 Cys and 2 Zn: Gal4 Zn fingers Many eukaryotic transcription factors Basic-leucine zipper proteins (hetero)Dimers, eukaryotic activators Helix-turn-helix

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a survey of dna binding domains
A survey of DNA binding domains
  • Zn -containing domains
    • 6 Cys and 2 Zn: Gal4
    • Zn fingers
    • Many eukaryotic transcription factors
  • Basic-leucine zipper proteins
    • (hetero)Dimers, eukaryotic activators
  • Helix-turn-helix
    • Many bacterial regulators, e.g. l repressor
    • Homeodomain proteins involved in segment determination in eukaryotes
  • Basic-helix-loop-helix proteins
    • (hetero)Dimers, differentiation factors
zinc fingers
Zinc fingers
  • Cys or His amino acids donate electron pairs to a tetrahedral configuration organized by a Zn++ ion
  • Several different types TFIIIA
    • C2H2 (e.g. TFIIIA)
    • C2C2 (e.g. Glucocorticoid receptor)
    • C6 (e.g. GAL4)
    • GATA
  • Different functions
    • DNA binding
    • Protein-protein interactions
  • Each finger contacts 3 consecutive bp in major groove
c2 c2 zn finger
C2-C2 Zn Finger
  • Found in steroid receptors
  • Glucocorticoid receptor
    • Three functions in central domain
      • DNA binding (Zn finger)
      • Dimerization (Zn finger)
      • Activation domain
    • C terminus binds steroid hormone
    • N terminus activates transcription

N

C

403

491

777

basic leucine zipper proteins
Basic-leucine zipper proteins

View down long axis of DNA

Lateral view of DNA

S. Harrison lab: cFos-cJun heterodimer, DBD, 2 complexes

Nature 1995 Jan 19;373(6511):257-61

Images via NCBI and their Cn3D program.

helix loop helix proteins
Helix-loop-helix proteins

Ma PC, Rould MA, Weintraub H, Pabo CO:

MyoD bHLH domain-DNA complex

Cell 1994 May 6;77(3):451-9

3 general types of activator domains
3 general types of activator domains
  • Acidic
    • Amphipathic helix, acidic amino acids on one face
    • No consistent secondary or tertiary structure has been identified
  • Glutamine-rich (Q-rich)
  • Pro-rich (P-rich)
no correspondence between type of dbd and type of ad
No correspondence between type of DBD and type of AD
  • Examples of proteins with acidic AD
    • GAL4 (Zn2Cys6)
    • AP1 (bZIP)
    • VP16 (no DBD)
    • l repressor (HTH)
  • Examples of proteins with Q-rich AD
    • Sp1 (Zn finger)
    • Antp (homeodomain)
    • Oct (POU-homeo)
lack of fixed structure in activator domains
Lack of fixed structure in activator domains
  • DBDs of transcription factors form discrete structures that can be analyzed by X-ray crystallography and NMR
  • The ADs do not generate identifiable electron density in the crystallographic analysis.
  • This indicates that they do not form discrete structures.
  • One hypothesis is that the ADs are unstructured until they interact with their targets.
  • This is an induced fit model.
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