Large T Antigen: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: === Introduction === The '''SV40 large tumor antigen''' is a multifunctional regulatory protein encoded by Simian Virus 40. It is classified under the AAA+ family of helicases <ref name="... |
No edit summary |
||
| Line 9: | Line 9: | ||
<Structuresection load='1tbd' side='right' caption='The origin binding domain of SV40 large T antigen' size='345' scene='User:Udayan_Shevade/Sandbox1/Origin_binding_domain_0/4'> | <Structuresection load='1tbd' side='right' caption='The origin binding domain of SV40 large T antigen' size='345' scene='User:Udayan_Shevade/Sandbox1/Origin_binding_domain_0/4'> | ||
===== The Origin Binding Domain ===== | ===== The Origin Binding Domain ===== | ||
The origin binding domain monomer consists of five anti-parallel beta sheets flanked on either side by a pair of alpha helices. The monomers assemble into a [http://www.pdb.org/pdb/explore/jmol.do?structureId=2FUF&bionumber=1 hexameric left-handed spiral], whose pitch complements the turn of DNA. Side-side interaction is necessary for hexamerization, in which residues <scene name='User:Udayan_Shevade/Sandbox1/Obd_183_185/1'>Phe183 and Ser185</scene> are crucial. Residues along the <scene name='User:Udayan_Shevade/Sandbox1/Obd_double_hexamer_residues/1'>B3 motif</scene> are necessary in the assembly of a double hexamer. A central pore is formed, large enough for dsDNA, carrying positive charge. A monomer is able to bind along a series of GAGGC pentanucleotides P1 through P4 at the origin, collectively known as Site II. <scene name='User:Udayan_Shevade/Sandbox1/Obd_residues/1'>Residues</scene> implicated in DNA binding are <scene name='User:Udayan_Shevade/Sandbox1/Obd_153_154_155/5'>Asn 153, Arg154, Thr155 from the A1 motif</scene>; <scene name='User:Udayan_Shevade/Sandbox1/Obd_203_204/1'>His203, Arg204 from the B2 motif</scene>; as well as <scene name='User:Udayan_Shevade/Sandbox1/Obd_201_202/1'>His201 andArg 202</scene><ref name="A"/>. The structural fold adopted by the fully assembled double hexamer is similarly conserved across a number of origin-binding proteins in different viruses, despite varying protein sequences, suggesting sequence-specificity. The Asn and Arg in the A1 motif primarily make up base-specific interactions with the DNA, whereas residues from the B2 loop interact mainly with the phosphate backbone. These specific interactions bury a large surface area of the protein and give rise to a 60nM K<sub>d</sub>.<ref name="C">PMID:1779811</ref>. | The origin binding domain monomer consists of five anti-parallel beta sheets flanked on either side by a pair of alpha helices. The monomers assemble into a [http://www.pdb.org/pdb/explore/jmol.do?structureId=2FUF&bionumber=1 hexameric left-handed spiral], whose pitch complements the turn of DNA. Side-side interaction is necessary for hexamerization, in which residues <scene name='User:Udayan_Shevade/Sandbox1/Obd_183_185/1'>Phe183 and Ser185</scene> are crucial. Residues along the <scene name='User:Udayan_Shevade/Sandbox1/Obd_double_hexamer_residues/1'>B3 motif</scene> are necessary in the assembly of a double hexamer. A central pore is formed, large enough for dsDNA, carrying positive charge. A monomer along this pore is able to bind along a series of GAGGC pentanucleotides P1 through P4 at the origin, collectively known as Site II. <scene name='User:Udayan_Shevade/Sandbox1/Obd_residues/1'>Residues</scene> implicated in DNA binding are <scene name='User:Udayan_Shevade/Sandbox1/Obd_153_154_155/5'>Asn 153, Arg154, Thr155 from the A1 motif</scene>; <scene name='User:Udayan_Shevade/Sandbox1/Obd_203_204/1'>His203, Arg204 from the B2 motif</scene>; as well as <scene name='User:Udayan_Shevade/Sandbox1/Obd_201_202/1'>His201 andArg 202</scene><ref name="A"/>. The structural fold adopted by the fully assembled double hexamer is similarly conserved across a number of origin-binding proteins in different viruses, despite varying protein sequences, suggesting sequence-specificity. The Asn and Arg in the A1 motif primarily make up base-specific interactions with the DNA, whereas residues from the B2 loop interact mainly with the phosphate backbone. These specific interactions bury a large surface area of the protein and give rise to a 60nM K<sub>d</sub>.<ref name="C">PMID:1779811</ref>. | ||
[[Image:Tagobd_dna_interactions.jpg|200px|left|thumb]] | [[Image:Tagobd_dna_interactions.jpg|200px|left|thumb]] | ||
Binding of large T antigen at the origin of replication allows replicative machinery to unwind and synthesize new DNA. Residues involved in DNA binding also bind ssDNA-binding protein human RPA<ref>PMID:2600586</ref>. T antigen also acts as a repressor of early gene transcription. When increased amounts of T antigen are present, it binds DNA and blocks the overlapping promoter sequence, thus behaving as its own regulator.</Structuresection> | Binding of large T antigen at the origin of replication allows replicative machinery to unwind and synthesize new DNA. Residues involved in DNA binding also bind ssDNA-binding protein human RPA<ref>PMID:2600586</ref>. T antigen also acts as a repressor of early gene transcription. When increased amounts of T antigen are present, it binds DNA and blocks the overlapping promoter sequence, thus behaving as its own regulator.</Structuresection> | ||
