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Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins.

Bozek K, Nakayama EE, Kono K, Shioda T - Front Microbiol (2012)

Bottom Line: However, the molecular determinants of this restriction mechanism are unknown.Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions.Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5).

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Informatics Saarbrücken, Germany.

ABSTRACT
Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus isolated from a macaque monkey (SIVmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm). Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh) monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239) is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5). As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

No MeSH data available.


Related in: MedlinePlus

Superposition of modeled structures of the N-terminal domains of HIV-2 GH123 (GH123, yellow) and SIVmac239 (red) capsid proteins. The three loops containing sites important for the TRIM5α interaction are numbered as follows: (1) N-terminal loop, (2) loop between α-helices 4 and 5 (L4/5), (3) loop between α-helices 6 and 7 (L6/7).
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Figure 2: Superposition of modeled structures of the N-terminal domains of HIV-2 GH123 (GH123, yellow) and SIVmac239 (red) capsid proteins. The three loops containing sites important for the TRIM5α interaction are numbered as follows: (1) N-terminal loop, (2) loop between α-helices 4 and 5 (L4/5), (3) loop between α-helices 6 and 7 (L6/7).

Mentions: We first constructed 3-D models of HIV-2 GH123 and SIVmac239 CA N-terminal domains by homology modeling. In the constructed models, HIV-2 GH123 and SIVmac239 CA N-terminal domains showed the most striking differences in shape of surface exposed loops (Figure 2). SIVmac239 CA is characterized by a more contracted shape as compared to the expanded loop structure of HIV-2 GH123. To confirm that this shape difference is not due to modeling noise, we remodeled both proteins using each one as a template for the other. The remodeled structures showed similar shape differences (data not shown), suggesting that the real structures differ.


Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins.

Bozek K, Nakayama EE, Kono K, Shioda T - Front Microbiol (2012)

Superposition of modeled structures of the N-terminal domains of HIV-2 GH123 (GH123, yellow) and SIVmac239 (red) capsid proteins. The three loops containing sites important for the TRIM5α interaction are numbered as follows: (1) N-terminal loop, (2) loop between α-helices 4 and 5 (L4/5), (3) loop between α-helices 6 and 7 (L6/7).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367459&req=5

Figure 2: Superposition of modeled structures of the N-terminal domains of HIV-2 GH123 (GH123, yellow) and SIVmac239 (red) capsid proteins. The three loops containing sites important for the TRIM5α interaction are numbered as follows: (1) N-terminal loop, (2) loop between α-helices 4 and 5 (L4/5), (3) loop between α-helices 6 and 7 (L6/7).
Mentions: We first constructed 3-D models of HIV-2 GH123 and SIVmac239 CA N-terminal domains by homology modeling. In the constructed models, HIV-2 GH123 and SIVmac239 CA N-terminal domains showed the most striking differences in shape of surface exposed loops (Figure 2). SIVmac239 CA is characterized by a more contracted shape as compared to the expanded loop structure of HIV-2 GH123. To confirm that this shape difference is not due to modeling noise, we remodeled both proteins using each one as a template for the other. The remodeled structures showed similar shape differences (data not shown), suggesting that the real structures differ.

Bottom Line: However, the molecular determinants of this restriction mechanism are unknown.Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions.Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5).

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Informatics Saarbrücken, Germany.

ABSTRACT
Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus isolated from a macaque monkey (SIVmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm). Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh) monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239) is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5). As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

No MeSH data available.


Related in: MedlinePlus