HIV-1
Protease Cleavage Sites
The protease
of HIV-1 is a small 99-amino acid aspartic enzyme that mediates the
cleavage of Gag, Gag-Pol and Nef precursor polyproteins. These
reactions occur late in the viral life cycle, during virion assembly
and maturation at the cell surface. The process is highly specific,
temporally regulated and essential for the production of infectious
viral particles (Jakes et al., Krausslich et al, Swanstrom et al.). In total twelve
proteolytic reactions
are required to generate a viable virion. Each reaction occurs at a
unique cleavage site that differs in amino acid composition (Billich et al.).
Cite the resource by citing the following paper:
de Oliveira T et al. Variability at HIV-1 Subtype C Protease Cleavage Sites: An Indication of Viral Fitness? Journal of Virology (2003), 77(17): 9422-30
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Choose
the protease
cleavage site for more information:
Proteins
Formed by Cleavage:
As
shown in the above figure, the main
structural proteins are formed by cleavage of the Pr55gag polyprotein
into matrix (MA, p17), capsid (CA, p24), nucleocapsid (NC, p7), p2, p1 , p6gag.
The viral enzymes
are
formed by cleavage of a second polyprotein, Pr160gag-pol,
a fusion protein derived by ribosomal frame shifting (13). Although
Pr160gag-pol also contains p17, p24 and p2, its C-terminal
cleavage products are NC, a transframe protein (TFP), p6pol,
protease (PR), reverse
transcriptase (RTp51), RT-RNase H
(RTp66) and integrase (IN)(Ikuta et al., Tessmer et al.).
HIV-1
Protease
Cleavage Site Amino Acid Sequences: |
Pr55gag
polyprotein clevage sites:
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|
1)MA/CA
(p17/p24)
M group MRCA
|
V
|
S
|
Q
|
N
|
Y
|
/
|
P
|
I
|
V
|
Q
|
N
|
Consensus M group
|
V
|
S
|
Q
|
N
|
Y
|
/
|
P
|
I
|
V
|
Q
|
N
|
HXB2 reference
|
V
|
S
|
Q
|
N
|
Y
|
/
|
P
|
I
|
V
|
Q
|
N
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
|
|
2) CA/p2
(p24/p2)
M group MRCA
|
K
|
A
|
R
|
V
|
L
|
/
|
A
|
E
|
A
|
M
|
S
|
Consensus M group
|
K
|
A
|
R
|
V
|
L
|
/
|
A
|
E
|
A
|
M
|
S
|
HXB2 reference
|
K
|
A
|
R
|
V
|
L
|
/
|
A
|
E
|
A
|
M
|
S
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
|
3) p2/NC
M group MRCA
|
S
|
T
|
A
|
I
|
M
|
/
|
M
|
Q
|
K
|
G
|
N
|
Consensus M group
|
x
|
x
|
A
|
I
|
M
|
/
|
M
|
Q
|
K
|
S
|
N
|
HXB2 reference
|
T
|
S
|
A
|
I
|
M
|
/
|
M
|
Q
|
R
|
G
|
N
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
|
|
4) NC/p1
M group MRCA
|
E
|
R
|
Q
|
A
|
N
|
/
|
F
|
L
|
G
|
K
|
I
|
Consensus M group
|
E
|
R
|
Q
|
A
|
N
|
/
|
F
|
L
|
G
|
K
|
I
|
HXB2 reference
|
E
|
R
|
Q
|
A
|
N
|
/
|
F
|
L
|
G
|
K
|
I
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
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|
5) p1/p6gag
M group MRCA
|
R
|
P
|
G
|
N
|
F
|
/
|
L
|
Q
|
S
|
R
|
P
|
Consensus M group
|
R
|
P
|
G
|
N
|
F
|
/
|
L
|
Q
|
S
|
R
|
P
|
HXB2 reference
|
R
|
P
|
G
|
N
|
F
|
/
|
L
|
Q
|
S
|
R
|
P
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
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6) NC/TFP
M group MRCA
|
E
|
R
|
Q
|
A
|
N
|
/
|
F
|
L
|
R
|
E
|
N
|
Consensus M group
|
E
|
R
|
Q
|
A
|
N
|
/
|
F
|
L
|
R
|
E
|
N
|
HXB2 reference
|
E
|
R
|
Q
|
A
|
N
|
/
|
F
|
L
|
R
|
E
|
N
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
|
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7)TFP/p6pol
M group MRCA
|
E
|
N
|
L
|
A
|
F
|
/
|
Q
|
Q
|
G
|
E
|
A
|
Consensus M group
|
E
|
N
|
L
|
A
|
F
|
/
|
x
|
Q
|
G
|
E
|
A
|
HXB2 reference
|
E
|
D
|
L
|
A
|
F
|
/
|
L
|
Q
|
G
|
K
|
A
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
|
|
8)p6pol/PR
M group MRCA
|
T
|
S
|
F
|
S
|
F
|
/
|
P
|
Q
|
I
|
T
|
C
|
Consensus M group
|
x
|
S
|
F
|
x
|
F
|
/
|
P
|
Q
|
I
|
T
|
C
|
HXB2 reference
|
V
|
S
|
F
|
N
|
F
|
/
|
P
|
Q
|
V
|
T
|
C
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
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9)PR/RTp51
M group MRCA
|
C
|
T
|
L
|
N
|
F
|
/
|
P
|
I
|
S
|
P
|
I
|
Consensus M group
|
C
|
T
|
L
|
N
|
F
|
/
|
P
|
I
|
S
|
P
|
I
|
HXB2 reference
|
C
|
T
|
L
|
N
|
F
|
/
|
P
|
I
|
S
|
P
|
I
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
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10)RT/RTp66
M group MRCA
|
G
|
A
|
E
|
T
|
F
|
/
|
Y
|
V
|
D
|
G
|
A
|
Consensus M group
|
G
|
A
|
E
|
T
|
F
|
/
|
Y
|
V
|
D
|
G
|
A
|
HXB2 reference
|
G
|
A
|
E
|
T
|
F
|
/
|
Y
|
V
|
D
|
G
|
A
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
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11) RTp66/INT
M group MRCA
|
I
|
R
|
K
|
V
|
L
|
/
|
F
|
L
|
D
|
G
|
I
|
Consensus M group
|
I
|
R
|
K
|
V
|
L
|
/
|
F
|
L
|
D
|
G
|
I
|
HXB2 reference
|
I
|
R
|
K
|
V
|
L
|
/
|
F
|
L
|
D
|
G
|
I
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
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12) Nef
M group MRCA
|
P
|
D
|
C
|
A
|
W
|
/
|
L
|
E
|
A
|
Q
|
E
|
Consensus M group
|
x
|
D
|
C
|
A
|
W
|
/
|
L
|
E
|
A
|
Q
|
E
|
HXB2 reference
|
A
|
A
|
C
|
A
|
W
|
/
|
L
|
E
|
A
|
Q
|
E
|
HXB2 numbering
|
Gag
protein:
|
|
complete
genome:
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References:
De Oliveira T,
Engelbrecht S,
Janse Van Rensburg E, Gordon M, Bishop K, Zur Megede J, Barnett
SW,Cassol S. 2003. Variability
at Human Immunodeficiency Virus Type 1 Subtype C Protease Cleavage
Sites: an Indication of Viral Fitness?Journal of Virology
77(17): pages 9422-9430,
Ikuta, K., S. Suzuki,
H.
Horikoshi, T. Mukai, and R. B.
Luftig. 2000. Positive and negative aspects of the human
immunodeficiency virus protease: development of inhibitors versus its
role in AIDS pathogenesis. Microbiol. Mol. Biol. Rev. 64:725-745. [Abstract/Free Full Text]
Jacks, T., M. D. Power, F. R. Masiarz, P. A. Luciw, P.
J.
Barr, H. E. Varmus. 1998. Characterization of ribosomal
frameshifting in HIV-1 gag-pol expression. Nature 331:280-283. [CrossRef]
Krausslich, H., F. H. Ingraham, M. Skoog, E. Wimmer,
P. V.
Pallai, and C. A. Carter. 1989. Activity of purified biosynthetic
proteinase of human immunodeficiency virus on natural substrates and
synthetic peptides. Proc. Natl. Acad. Sci. USA 86:807-811. [Medline]
Swanstrom, R., and J. W. Wills. 1997. Retroviral
gene
expression. II. Synthesis, processing, and assembly of viral proteins,
p. 263-334. In J. M. Coffin, S. H. Hughes, and H. E. Varmus
(ed.), Retroviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor,
N.Y.
Billich, S., M. T. Knoop, J. Hansen, P. Strop, J.
Sedlacek,
R. Mertz, and K. Moelling. 1988. Synthetic peptides as substrates
and inhibitors of human immunodeficiency virus-1 protease. J. Biol.
Chem. 263:17905-17908. [Abstract/Free Full Text]
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