Lecture 10 - Modular mechanisms of transcription activation and repression Flashcards
what is a zinc-figer motif
protein regions that fold around a central Zn2+ ion.
2 zinc finger motifs and their occurence
C2H2 zinc finger –> most common motif in humans
C4 zinc finger –> found in approx. 50 human TFs
What are C and H in C2H2 and C4 zinc fingers
a.a cystine and histidine
C2H2 zinc finger how it works, how many of this motif the domain contains, how domain/prot. bind
Binding of 2 C and 2 H to zinc compacts the domain and allows insertion of alpha helix in the major groove.
Usually domain contains 3 or more C2H2 motifs
Motifs bind as monomers
C4 zinc finger how many of this motif the domain contains, how domain/prot binds.
Domain contains only two motifs
Binds as homodimers. Note : like C2H2, fingers insert in DNA
Something particular about binding of domains that have C4 zinc finger motif
Domains have two-fold rotational symmetry and bind to consensus DNA sequences that are inverted repeats.
2 other DNA binding domains
leucine zipper. basic helix-loop-helix (bHLH)
Leucine zipper motif. Leucine characteristic. and consequence
Leucine residue at every seventh position. Leucine is hydrophobic so goes inwards and gives helical form to helices of zipper
How leucine zipper binds DNA
as dimers, often heterodimers
Proteins like leucine zipper principle and how you call them
'’Basic zipper (bZip)’’ is the name of the larger family. Prots in this family have a zipper with a different hydrophobic a.a at every seventh position
basic helix-loop-helix description (diff. w/ basic zipper)
similar to basic zipper but a nonhelical loop seperates two alpha-helical regions.
How bHLH containing proteins bind
Bind as heterodimers
Activation domain a.a usually found
usually high percentage of one or two a.a (Asp, Glu, Gln, Pro, Ser, Thr)
Acidic activation domain what it’s made of and something particular
high percentage of Asp or Glu and is active when bound by a coactivator
Ex. of acidic activation domains (2)
1) RARgamma has to bind retinoic acid to be in an active conformation
2) CREB must be phosphorylated to bind its coactivator CBP and become an active TF.
Activation domains before they bind co-activator
may be random coils/unstructured
Other exemple of act. domain w/ coactivator and how it works
Estrogen receptor ligand-binding activation domain When estrogen (grey) binds activation domain (brown), a green alpha helix interacts with the ligand (domain -> brown). Alpha helix of domain bends and can bind alpha helix subunit of another coactivator
Repressor of estrogen binding in estrogen receptor ligand binding activation domain
Tamoxifen. Blocks binding of estrogen. Domain can’t become active
Length of repression domains (and activation domains)
may be short (<15 a.a.)
Repression domains, 2 (obvious) things it does
Binds co-repressor proteins and mediates protein-protein interaction.
Repressors and activators DNA binding in common (2 things to note)
1) Certain repressors can block activators by binding to their DNA sequence
2) Repressors and activators can bind to common sequences or have their specific sequences
Exemple of repressor and how it interacts with DNA
Bacteriophage 434. Helix interacts with MAJOR groove
Why are TFs required
basal transcription is very low
3 things that can generate transcription factor regulatory diversity
Heterodimers, Inhibitory factors, Cooperative binding of unrelated TFs to nearby sites
