Gag polyprotein

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{{STRUCTURE_1baj| PDB=1baj | SIZE=300| SCENE= |right| CAPTION=HIV-1 Gag polyprotein C-termianl, [[1baj]] }}
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<StructureSection load='2wlv' size='350' side='right' caption='Gag polyprotein N-terminal capsid domain of HIV-2 (PDB entry [[2wlv]])' scene=''>
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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]].
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== Function ==
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{{TOC limit|limit=2}}
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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]].
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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.
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==3D structures of factor IX==
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==Capsid (CA) Domain==
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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.
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''Updated November 2011''
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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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===Gag polyprotein from HIV-1===
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As a side effect of the β-hairpin formation, the helix 6 is displaced by approximately 2-Angstroms. This displacement, though structurally minor, causes significant biological changes in the protein. Most importantly, helix 6 interacts with the protein cyclophilin A (CypA)-binding site. CypA is a prolyl isomerase and chaperone protein involved in the infection process by aiding in unpacking the capsid <ref>PMID:8648689</ref><ref>PMID:7969495</ref><ref>PMID:9420228</ref>.
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[[2h3i]] – Gag residues 2-132 – HIV-1<BR />
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==Implications==
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[[2h3f]], [[2h3i]], [[1uph]] - Gag residues 2-132 – NMR<BR />
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HIV-1 viral particles need to form a capsid cone-like structure prior to infection of the host cell. The protealytic cleavage of the immature Gag<sup>283</sup> polyprotein results in a capsid domain. This post-translational modification is essential to the formation of the core structure. Many studies have shown that the β-hairpin formed after maturation is essential for the capsid core particle formation <ref name="gitti"/><ref name="von"/>. As a result of the β-hairpin formation, the helix 6 is displaced causing an allosteric mechanism for CpyA binding. Overall, the maturation of Gag<sup>283</sup> and formation of the mature CA protein is essential for core capsid particle creation and consequently final infection.
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[[1l6n]] - Gag residues 1-283 – NMR<BR />
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[[1gwp]] - Gag residues 132-283 – NMR<BR />
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[[2jmg]], [[2nv3]] - Gag residues 2-132 (mutant) – NMR<BR />
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[[1u57]] - Gag residues 1-48 – NMR<BR />
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[[1esk]] - Gag residues 12-53 – NMR<BR />
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[[1baj]] – Gag C terminal<BR />
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[[2znf]] – Gag zinc fingerlike domain]] - NMR<BR />
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[[2h3q]], [[2h3v]], [[2h3z]] - Gag residues 2-132 + phosphatidyl inositol bisphosphate - NMR<BR />
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[[1mt7]], [[1mt8]] – Gag MA-CA cleavage site + protease retropepsin (mutant) <BR />
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[[1agb]], [[1agc]], [[1agd]], [[1age]], [[1agf]] – Gag peptide + β-2 microglobulin + B*0801<BR />
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[[3p9g]], [[3p9h]], [[3obu]], [[3obx]], [[1m4p]], [[1m4q]] - Gag peptide + tumor susceptibility gene 101 protein N terminal<BR />
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[[1fgl]] – Gag residues 81-105 + cyclophilin A<BR />
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[[2xde]] - Gag residues 1-146 + inhibitor<BR />
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[[2x2d]] - Gag residues 133-278 + peptidyl-prolyl cis-trans isomerase A<BR />
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[[2lf4]] - Gag residues 133-363 (mutant)<br />
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[[2xt1]] – Gag C terminal + camelid VHH<br />
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[[1sje]], [[1sjh]] – Gag peptide + HLA-DR1<BR />
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[[1kj4]], [[1kj7]], [[1kjf]], [[1kjg]] - Gag peptide + POL polyprotein
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===Gag polyprotein from HIV-2===
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==3D structures of Gag polyprotein==
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[[Gag polyprotein 3D structures]]
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[[2wlv]] - Gag residues 99-242 – HIV-2<BR />
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</StructureSection>
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[[2ec7]] – Gag – NMR<BR />
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===Gag polyprotein from Rous sarcoma virus===
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==Additional Resources==
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For additional information, see: [[Human Immunodeficiency Virus]]
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<br />
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[[3g0v]], [[3g1g]], [[3g21]], [[3g1i]] - Gag C terminal – Rous sarcoma virus<BR />
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==Reference==
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[[3g26]], [[3g28]], [[3g29]] - Gag C terminal (mutant) <BR />
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[[1p7n]] – Gag N terminal<BR />
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[[1em9]] - Gag N terminal – NMR<BR />
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[[1eoq]] - Gag C terminal – NMR<BR />
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[[1a6s]] – Gag M domain (mutant) - NMR<BR />
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===Gag polyprotein from Simian immunodeficiency virus===
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<references/>
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[[1ecw]], [[1ed1]] - Gag<BR />
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==Team from University of Missouri, Columbia, MO==
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[[2xs1]] - Gag peptide + programmed cell death 6-interacting protein
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===Gag polyprotein from Moloney murine leukemia virus===
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:Students: Zheng Wang, Allison Tegge, Xin Deng
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:Advisors: Jianlin Cheng, PhD, Department of Computer Science, Informatics Institute, the Life Science Center, Interdisciplinary Plant Group, University of Missouri, Columbia
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[[1u7k]] - Gag residues 215-345<BR />
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:Mentor: Chun Tang, PhD, Department of Biochemistry, University of Missouri, Columbia
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[[1u6p]] – Gag fragment + DNA – Moloney murine leukemia virus
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===Gag polyprotein from equine infectious anemia virus===
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[[1hek]] – Gag
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===Gag polyprotein from Mason-Pfizer monkey virus===
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[[1cl4]] - Gag residues 49-80 (mutant) – NMR<BR />
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==NMR Equipment and the Authors==
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<gallery>
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Image:Cheng_casp8.jpg | Dr. Jianlin Cheng
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Image:NMR_sample.JPG | Protein sample
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Image:Chun_Tang.JPG | Dr. Chun Tang
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Image:1gwp_people1.JPG | Labmates
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Image:1gwp_people2.JPG | Labmates
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</gallery>
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'''Created by [[User:Allison Tegge|Allison Tegge]] and [[User:David Canner|David Canner]]'''

Current revision

Gag polyprotein N-terminal capsid domain of HIV-2 (PDB entry 2wlv)

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Contents

Additional Resources

For additional information, see: Human Immunodeficiency Virus

Reference

  1. ↑ Coffin, J., S. Hughes, and H. Varmus, Retroviruses. 1997: Cold Spring Harbor Laboratory Press.
  2. ↑ 2.0 2.1 Gitti RK, Lee BM, Walker J, Summers MF, Yoo S, Sundquist WI. Structure of the amino-terminal core domain of the HIV-1 capsid protein. Science. 1996 Jul 12;273(5272):231-5. PMID:8662505
  3. ↑ 3.0 3.1 von Schwedler UK, Stemmler TL, Klishko VY, Li S, Albertine KH, Davis DR, Sundquist WI. Proteolytic refolding of the HIV-1 capsid protein amino-terminus facilitates viral core assembly. EMBO J. 1998 Mar 16;17(6):1555-68. PMID:9501077 doi:10.1093/emboj/17.6.1555
  4. ↑ Braaten D, Franke EK, Luban J. Cyclophilin A is required for an early step in the life cycle of human immunodeficiency virus type 1 before the initiation of reverse transcription. J Virol. 1996 Jun;70(6):3551-60. PMID:8648689
  5. ↑ Thali M, Bukovsky A, Kondo E, Rosenwirth B, Walsh CT, Sodroski J, Gottlinger HG. Functional association of cyclophilin A with HIV-1 virions. Nature. 1994 Nov 24;372(6504):363-5. PMID:7969495 doi:http://dx.doi.org/10.1038/372363a0
  6. ↑ Ackerson B, Rey O, Canon J, Krogstad P. Cells with high cyclophilin A content support replication of human immunodeficiency virus type 1 Gag mutants with decreased ability to incorporate cyclophilin A. J Virol. 1998 Jan;72(1):303-8. PMID:9420228

Team from University of Missouri, Columbia, MO

Students: Zheng Wang, Allison Tegge, Xin Deng
Advisors: Jianlin Cheng, PhD, Department of Computer Science, Informatics Institute, the Life Science Center, Interdisciplinary Plant Group, University of Missouri, Columbia
Mentor: Chun Tang, PhD, Department of Biochemistry, University of Missouri, Columbia

NMR Equipment and the Authors

Dr. Jianlin Cheng

Protein sample

Dr. Chun Tang

Labmates

Labmates

Created by Allison Tegge and David Canner

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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