Motifs are regulatory protein domains that bind to DNA and control transcription. The main motifs are zinc finger, helix-turn-helix, and leucine zipper. Zinc finger motifs use zinc atoms to stabilize finger-like structures that bind to DNA. Helix-turn-helix motifs contain two alpha helices separated by a beta turn that bind in the DNA major groove. Leucine zipper motifs allow two alpha helices to dimerize via leucine residues, binding DNA and proteins. These motifs allow precise protein-DNA interactions that regulate transcription.

1. MOTIFS

4.  Means dominant element.
 Act as regulatory proteins.
 Motif in proteins mediate the binding of regulatory
proteins (Transcription Factor) to DNA.
 Transcription is controlled with help of regulatory
proteins.
 The DNA binding site for regulatory proteins are
often inverted repeats of short DNA sequences (A
palindrome).
 Proteins interact with steroids and other hormones
that diffuse through the cell membrane by motif.
DNA BINDING MOTIFS

5.  Motifs bind with high affinity to specific site
Low affinity with other part of DNA.
Interaction maintained by hydrogen bonds
& van der waals force.
Motif are four in no.
- Zinc finger Motif
- Leucine zipper Motif
- Helix turn helix Motif
- Helix loop helix Motif
- Occur specific protein –DNA interactions

6. HELIX TURN HELIX MOTIF(HTH)
 Consists of about 20 a.a. in three α
helicals segments
Each α-helical 7-9 a.a. long separated
by a β turn.
The α3 helices form the DNA recognition
surface, and the rest of the molecule
appears to be involved in stabilizing these
structures.
When bound to DNA this recognition
helix is positioned in or nearly in the
major groove of DNA.

7. The average diameter of an α helix is 1.2
nm, which is the approximate width of the
major groove in the B form of DNA
In bacteria, the helix-turn-helix motif is
commonly found in repressor proteins and is
about 20 amino acids long.
They are common in proteins that regulate
developmental processes
Eg:- lactose repressor
Cap

10. ZINC FINGER MOTIF
The zinc finger was the second DNA binding
motif.
 About 30a.a. form an elongated loop, held
together by a single zn which is coordinated
to 4 of the residues: 4 cys or 2 cys & 2 his.
 Binds with zinc tetrahedral structure ,
antiparallel two-stranded β-sheets and an α-
helix.
 Interaction with single zn finger is week &
many proteins have many zn fingers which
enhance binding.

11.  example :- TFIIIA (transcription factor)
The protein TFIIIA, a positive regulator
of RNA transcription, required zinc for
activity.
Each TFIIIA molecule contains nine
zinc ions in a repeating coordination
complex formed by closely spaced
cysteine-cysteine residues followed
12–13 amino acids later by a histidine-
histidine pair.

15. EXAMPLE :- GLUCOCORTICOID
Proteins interact with steroids and other
hormones that diffuse through the cell
membrane.
A dimer of the zinc finger domain of the
glucocorticoid receptor (belonging to
intracellular receptor family) bound to
its specific DNA sequence.
Zinc atoms stabilizing DNA-binding
Helix and dimerization interface .

16. 2. THE GLUCOCORTICOID (NUCLEAR)
RECEPTOR IS FOUND IN THE CYTOPLASM

17. PROTEIN PROTEIN INTERACTION
DOMAIN
 Regulatory Proteins also have domains
for interaction with other proteins eg :
RNA Polymerase etc.
These are mainly of two types:
1. Leucine Zipper
2. Basic Helix Loop Helix motif.

18.  b refers to basic region in each domain that forms
the majority of the DNA-binding motif
 30-amino-acid sequence in the carboxyl terminal
region of the enhancer binding protein (rich in
leucine a.a).
 The basic leucine zipper domain contains an
alpha helix with a leucine at every 7th amino acid.
 If two such helices find one another, the leucines
can interact as the teeth in a zipper, allowing
dimerization of two proteins.
 This occurs for eight helical turns and four leucine
repeats.
BZIP – LEUCINE ZIPPERS

19. This structure allows two identical
monomers or heterodimers to “zip together”
in a coiled coil and form a tight dimeric
complex .
This protein-protein interaction may serve
to enhance the association of the separate
DNA binding domains with their target.
Eg:- enhancer binding proteins – fos & jun.
It regulates gene expression.

20. Leucine Zipper Dimer
Same motif mediating both DNA binding and
Protein dimerization

22. 1. Parallel coiled-coil structure
2. Note that the leucines are spaced 7 aa
apart.

23.  Occur in some eukaryotic regulatory proteins
 Control gene expression.
 proteins share conserved region of 50 a.a.
important in both DNA binding & protein
dimerization.
 This region can form two short alpha helices
linked by loop of variable length & bind to DNA.
 Motif of two polypeptides interact to form dimers.
 DNA gripped the same way as in the leucine
zipper.
HELIX-LOOP-HELIX (HLH )