Gag polyprotein: Difference between revisions

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[[Image:1gwp.png|left|200px|thumb|The mature CA<sup>N</sup> domain of the [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_12) HIV-1] Gag<sup>283</sup> polyprotein ([[1gwp]]), is a protein involved in formation of the capsid core particle. The structure of the CA<sup>N</sup> domain was determined through [[NMR]] by Tang et al. <ref name="source">PMID:12032547</ref>.]]
<StructureSection load='2wlv' size='350' side='right' caption='Gag polyprotein N-terminal capsid domain of HIV-2 (PDB entry [[2wlv]])' scene=''>
{{STRUCTURE_1gwp|  PDB=1gwp  |  SCENE= }}
 
The '''Gag polyprotein''' (Gag) is part of the basic infrastructure of retroviruses.  The Gag is processed during maturation of matrix protein, capsid protein, spacer peptide and nucleocapsid protein.  For detailed discussion of HIV-1 Gag polyprotein see [[Hiv-1 gag]].  
== Function ==
 
The '''Gag polyprotein''' (Gag) is part of the basic infrastructure of retroviruses.  The Gag is processed during maturation to '''matrix protein (MA)''', '''capsid protein (CA)''', '''spacer peptides (SP1, SP2)''', '''nucleocapsid protein (NC)''' and '''p6'''.  For detailed discussion of HIV-1 Gag polyprotein see [[Hiv-1 gag]].  


Gag of [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_12) human immunodeficiency virus type 1] (HIV-1), is a primary protein involved in the packaging of two copies of the viral genome for capsid formation <ref>Coffin, J., S. Hughes, and H. Varmus, Retroviruses. 1997: Cold Spring Harbor Laboratory Press.</ref>. In the cytoplasm of the infected cell, Gag is translated and approximately 1500 copies of the immature HIV-1 Gag polyprotein [[1l6n]] come together to form an immature viral particle. After budding of the viral particle, viral proteases cleave the Gag protein into three structurally different products: the matrix, the capsid, and the nucleocapsid. The protealytic cleavage results in viral maturation and induces significant structural changes of the protein products. Following this proteolysis, the viral particle takes on the classic cone shape required for a new infection.
Gag of [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_12) human immunodeficiency virus type 1] (HIV-1), is a primary protein involved in the packaging of two copies of the viral genome for capsid formation <ref>Coffin, J., S. Hughes, and H. Varmus, Retroviruses. 1997: Cold Spring Harbor Laboratory Press.</ref>. In the cytoplasm of the infected cell, Gag is translated and approximately 1500 copies of the immature HIV-1 Gag polyprotein [[1l6n]] come together to form an immature viral particle. After budding of the viral particle, viral proteases cleave the Gag protein into three structurally different products: the matrix, the capsid, and the nucleocapsid. The protealytic cleavage results in viral maturation and induces significant structural changes of the protein products. Following this proteolysis, the viral particle takes on the classic cone shape required for a new infection.


==Capsid (CA) Domain==
==Capsid (CA) Domain==
Overall, the mature CA<sup>N</sup> domain is very similar in structure to the corresponding domain of the immature Gag<sup>283</sup> polyprotein <ref name="source" />. The CA<sup>N</sup> protein contains 7 α-helices (helix 1-helix 7) that pack together to form a triangular shape, which helps facilitate the final complex formation for the capsid core particles. There are two significant structural differences between the immature and mature versions of the CA<sup>N</sup> domain: an N-terminal β-hairpin and a 2-Angstrom displacement of helix 6.
Overall, the mature CA<sup>N</sup> domain is very similar in structure to the corresponding domain of the immature Gag<sup>283</sup> polyprotein. The CA<sup>N</sup> protein contains 7 α-helices (helix 1-helix 7) that pack together to form a triangular shape, which helps facilitate the final complex formation for the capsid core particles. There are two significant structural differences between the immature and mature versions of the CA<sup>N</sup> domain: an N-terminal β-hairpin and a 2-Angstrom displacement of helix 6.


In the mature CA<sup>N</sup> protein, the N-terminal residues form an anti-parallel β-hairpin instead of the random coil that is observed when the same residues are compared in the immature Gag<sup>283</sup> polyprotein. The NH<sub>2</sub>+ group of the N-terminus proline establishes a salt bridge with a nearby aspartic acid, which stabilizes the β-hairpin. This N-terminal β-hairpin is required for the final formation of the viral capsid, and many studies have shown through conservation and mutagenesis that this β-hairpin is responsible for the stabilization of the protein complexes involved in the capsid formation <ref name="gitti">PMID:8662505</ref><ref name="von">PMID:9501077</ref>.  
In the mature CA<sup>N</sup> protein, the N-terminal residues form an anti-parallel β-hairpin instead of the random coil that is observed when the same residues are compared in the immature Gag<sup>283</sup> polyprotein. The NH<sub>2</sub>+ group of the N-terminus proline establishes a salt bridge with a nearby aspartic acid, which stabilizes the β-hairpin. This N-terminal β-hairpin is required for the final formation of the viral capsid, and many studies have shown through conservation and mutagenesis that this β-hairpin is responsible for the stabilization of the protein complexes involved in the capsid formation <ref name="gitti">PMID:8662505</ref><ref name="von">PMID:9501077</ref>.  
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==3D structures of Gag polyprotein==
==3D structures of Gag polyprotein==
[[Gag polyprotein 3D structures]]


''Updated November 2011''
</StructureSection>
 
===Gag polyprotein from HIV-1===
 
[[2h3i]] – Gag residues 2-132 – HIV-1<BR />
[[2h3f]], [[2h3i]], [[1uph]] - Gag residues 2-132 – NMR<BR />
[[1l6n]] - Gag residues 1-283 – NMR<BR />
[[1gwp]] - Gag residues 132-283 – NMR<BR />
[[2jmg]], [[2nv3]] - Gag residues 2-132 (mutant) – NMR<BR />
[[1u57]] - Gag residues 1-48 – NMR<BR />
[[1esk]] - Gag residues 12-53 – NMR<BR />
[[1baj]] – Gag C terminal<BR />
[[2znf]] – Gag zinc fingerlike domain]] - NMR<BR />
[[2h3q]], [[2h3v]], [[2h3z]] - Gag residues 2-132 + phosphatidyl inositol bisphosphate - NMR<BR />
[[1mt7]], [[1mt8]] – Gag MA-CA cleavage site + protease retropepsin (mutant) <BR />
[[1agb]], [[1agc]], [[1agd]], [[1age]], [[1agf]] – Gag peptide + β-2 microglobulin + B*0801<BR />
[[3p9g]], [[3p9h]], [[3obu]], [[3obx]], [[1m4p]], [[1m4q]] - Gag peptide + tumor susceptibility gene 101 protein N terminal<BR />
[[1fgl]] – Gag residues 81-105 + cyclophilin A<BR />
[[2xde]] - Gag residues 1-146 + inhibitor<BR />
[[2x2d]] - Gag residues 133-278 + peptidyl-prolyl cis-trans isomerase A<BR />
[[2lf4]] - Gag residues 133-363 (mutant)<br />
[[2xt1]] – Gag C terminal + camelid VHH<br />
[[1sje]], [[1sjh]] – Gag peptide + HLA-DR1<BR />
[[1kj4]], [[1kj7]], [[1kjf]], [[1kjg]] - Gag peptide + POL polyprotein
 
===Gag polyprotein from HIV-2===
 
[[2wlv]] - Gag residues 99-242 – HIV-2<BR />
[[2ec7]] – Gag – NMR<BR />
 
===Gag polyprotein from Rous sarcoma virus===
 
[[3g0v]], [[3g1g]], [[3g21]], [[3g1i]] - Gag C terminal – Rous sarcoma virus<BR />
[[3g26]], [[3g28]], [[3g29]] - Gag C terminal (mutant) <BR />
[[1p7n]] – Gag N terminal<BR />
[[1em9]] - Gag N terminal – NMR<BR />
[[1eoq]] - Gag C terminal – NMR<BR />
[[1a6s]] – Gag M domain (mutant) - NMR<BR />
 
===Gag polyprotein from Simian immunodeficiency virus===
 
[[1ecw]], [[1ed1]] - Gag<BR />
[[2xs1]] - Gag peptide + programmed cell death 6-interacting protein
 
===Gag polyprotein from Moloney murine leukemia virus===
 
[[1u7k]] - Gag residues 215-345<BR />
[[1u6p]] – Gag fragment + DNA – Moloney murine leukemia virus
 
===Gag polyprotein from equine infectious anemia virus===
 
[[1hek]] – Gag
 
===Gag polyprotein from Mason-Pfizer monkey virus===
 
[[1cl4]] - Gag residues 49-80 (mutant) – NMR<BR />


==Additional Resources==
==Additional Resources==
Retrieved from "https://proteopedia.org/Gag_polyprotein"