1. Structure and Function Laura Martin
HIV Integrase (IN)
Structure and Function
Laura Martin

3. Structure
Three domains- the catalytic core, the C- terminal and N-terminal domains
Catalytic core – contains active site responsible for catalysis of integration rxn
C- terminal- binds both viral and host DNA
N- terminal- unknown, but has zinc binding motif suggesting nucleic acid interaction3

4. HIV Integrase N CORE C (1-49) (50-212) (213-288) D-X(39-58)-D-X35-E
H12 H16
C40 C43
D64
D116
E152 N
CORE C
(1-49)
(50-212)
( )

5. HIV Integrase
N-terminus
Core
C-terminus

6. Structure of HIV Integrase
Full length enzyme (1-288 a.a)
Catalytic core ( a.a)
C-terminal domain ( a.a)
N-terminal domain (1-51 a.a)

7. Structure of Catalytic Core Domain
Central 5 stranded Beta- sheet with six surrounding helices
-3 highly conserved
residues (D64,D116, E152)

8. Why HIV Integrase is important!
Total: 34 – 46 million
Western Europe –
North Africa & Middle East –
Sub-Saharan Africa
25.0 – 28.2 million
Eastern Europe & Central Asia
1.2 – 1.8 million
South
& South-East Asia
4.6 – 8.2 million
Australia
& New Zealand –
North America
– 1.2 million
Caribbean –
Latin America
1.3 – 1.9 million
East Asia & Pacific
– 1.3 million

9. Primary Structure of the Catalytic Domain

10. The N-terminal Domain -Conserved HHCC motif that binds Zinc
-Probably functions in
Multimerization
-DNA Binding

11. DNA Binding Domain -Dimer -Each monomer is constructed of 5 stranded
beta-barrel
-Hydrophobic interactions
between two, 3 stranded
beta sheets

12. Integrase has NLS Pre-Integration Complex Integration Reverse
transcription
Pre-Integration
Complex
Nuclear
import
Integration

13. Function
Responsible for covalent recombination of retroviral DNA with host cell chromosomal DNA within nucleus
Integration catalyzed by HIV integrase
Integrase performs a series of DNA cutting and joining
First removes two nucleotides from each 3’ end of viral DNA
Second step- strand transfer- joins 3’ ends to 5’ ends of strands of target DNA at integration site

14. HIV Integration Target DNA Viral DNA Provirus (2) Strand Transfer5’ AC CA
(1) 3’-end processing
(2) Strand Transfer
HO-
-OH
Provirus
(3) 5’-end joining

15. Sources King, Peter Powerpoint: HIV, AIDS, Integrase and You
Pieribone, Ph.d, Vincent. "HIV Integrase: A New Therapeutic Target." Treatment Issues (1995). 8 Nov <
Robert, Cragie. "HIV Integrase, a Brief Overview from Chemistry to Therapeutics." Journal of Biological Chemistry (2001). 8 Nov <
Subhendu Chakraborti Power Point presentation: HIV Integrase Last but not least
Walsh, Matthew B., and Marcey David. "HIV- 1 Integrase The Catalytic Core Domain and Minimal DNA Binding Domain." (2001). 8 Nov <