The document discusses the DNA binding domain known as the helix-turn-helix structure. It contains two alpha helices joined by a turn that interacts with DNA in the major groove through charged amino acids on the recognition helix. The helix-turn-helix motif can function in both gene activation and repression by changing its conformation through modifications or allosteric binding, thereby changing the DNA bending and accessibility of transcriptional machinery. Examples given are the lac repressor, which bends DNA and prevents transcription until binding lactose, and the catabolite activator protein (CAP), which activates transcription after cAMP binding causes a conformational change in the helix-turn-helix motif.

1. DNA binding domain
with Helix turn Helix
structures
Naveed asif (MS)
Biochemistry
COMSATS-Islamabad
Pakistan
2013-14
It’s a DOMAIN that binds to DNA

2. •The proteins that Bind to DNA consist of
fallowing parts
1-Ligend binding Domain
3-Activation or repression
Domain (C-terminal)
2-DNA binding Domain
(N-terminal)

3. •Presentation constitutes
1-Structure of Helix turns Helix
Domain
2-Its interaction with DNA
3-Its Functions
a-In Activators
b-In Repressors

4. •1-Sturcture of Helix turn Helix
Domain
Secondary structure (Helix) + Secondarystructure(Helix)
Supersecondary structure (motif)
Mofit + Motif
Domain

5. •Structure of helix turn helix motif
Two alpha helixes joined by a turn
DIFFERENCE between turn & loop

6. •Structure of a loop
Difference
1-Loop is larger than turn. 2-loop has 7 to 16 amino acids. turn has 4 to 6
amino acids
Similarities
Both has charged amino acids

7. •General Mechanism of formation of
a Domain
Secondary structure (Helix or Beta) + Secondary structure (HelixorBeta)
Supersecondary structure (motif)
Mofit + Motif
Domain

8. •Formation of Complex Domains

9. •BACK to helix turn helix motif
e.g. HOMEO-DOMAIN
They are formed by homeoboxes.
Homeoboxes are conserved sequences of
180 base pairs; the proteins formed by these
boxes give rise to domains that are called
homeodomains

10. •Mechanism of
interaction with DNA
PARTS of HELIX turn HELIX motif
1-HORIZONTAL one is
recognition helix
ANGEL 90
2-VETICAL helix is going to
interact with back bone
3-Recognition helix goes into the
major groove
C-terminal (Recognition helix) andN terminal (helix that interact with
backbone)

11. •Mechanism Cont.
Interaction is between charged
amino acids, phosphate back
bone and nitrogenous bases
Arginine (positively charged),
Asparagines-Asn (neutral) and
serine-Ser (neutral)
THIS BINDING COULD BE
OF ACTIVATOR HTH motif

12. •Mechanism cont.
HTH-Motif(Charge on Amino Acids)
CHARGE on the AMINO ACID plays the key role
Neutral, (--) and (+)
1-This untimely effect the polypeptide polarity
2-this also gives a sequence specific binding between DNA &
Protein
And can be modified
1-Phosphorilation
2-Aceylation
3-methylation
These modifications are very important in activator and
repressor proteins

13. •Functions
Transcription Repression & Activation
1-Repression function of helix turn helix motif
2-Activation function of helix turn helix motif
e.g.:- Lac repressor &CAP(catabolite activator protein)

14. •Lac repressor (helix turn helix motif)
SEQUENCE
Glutamic acid (negative charge)
Asparagines(neutral)
Leucine(neutral)
Under the normal circumstances
repressor keeps on binding the
operator.
It BENDS the DNA
What type of bending?
No Transcription.
Lactose→ Allolactose
Allolactose binds to the allostaric
site→ Conformational change
What kind of change? The
distance between the two helix’s
changes
Now repressor is unable to bind
leading to transcription
•
•
•
Normal
DNA
↓
bending
•
↓
Bending
•
↓
•
↓

15. •2-CAP (Catabolite Activator Protein)
helix turn helix Motif
SEQUENCE
Arginine (Positively charged)
Asparagines (neutral)
Serine (neutral)
cAMP INTERACTION
Mechanism
CAP+cAMP
Confirmation change in the
CAP Protein
What change?
Distance between the two
helix’s changes
Now DNA bends
Activates the Transcription
•
•
•
•
•
Normal
DNA
↓
Open bend
↓

16. Thanks for your
PATEINCE
References
Molecular genetics lectures, Dr. Saeed
COMSATS-Islamabad, Pakistan
Biosciences resource; Massey University, New Zealand
Ishaque P.K , Pondicherry University