Sandbox Reserved 1076: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
{{Sandbox_Reserved_Butler_CH462_Sp2015_#}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | {{Sandbox_Reserved_Butler_CH462_Sp2015_#}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | ||
=EspG5 Secretion Protein= | |||
==Introduction== | ==Introduction== | ||
EspG is a key secretion protein involved with the virulence of [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis'']. The specificity of EspG binding affinity to its specific [http://proteopedia.org/wiki/index.php/PE/PPE_Protein_Complex PE-PPE] ligand has many contributing factors. The four different [http://proteopedia.org/wiki/index.php/4w4i EspG] proteins found in ''Mycobacterium tuberculosis'' have different characteristics that influence binding, where EspG5 binds to the most PE-PPE proteins. Not all EspG proteins bind to the same ligand; specific interactions from specific residue interactions, electrostatics, steric hinderance and concavity of the EspG binding pocket influence binding. The EspG PE-PPE complex is to be excreted in the [http://en.wikipedia.org/wiki/CFP-10 ESAT-6 pathway], this pathway is an attractive target for inducing apoptosis in Mtb, this makes it a good drug target. | EspG is a key secretion protein involved with the virulence of [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis'']. The specificity of EspG binding affinity to its specific [http://proteopedia.org/wiki/index.php/PE/PPE_Protein_Complex PE-PPE] ligand has many contributing factors. The four different [http://proteopedia.org/wiki/index.php/4w4i EspG] proteins found in ''Mycobacterium tuberculosis'' have different characteristics that influence binding, where EspG5 binds to the most PE-PPE proteins. Not all EspG proteins bind to the same ligand; specific interactions from specific residue interactions, electrostatics, steric hinderance and concavity of the EspG binding pocket influence binding. The EspG PE-PPE complex is to be excreted in the [http://en.wikipedia.org/wiki/CFP-10 ESAT-6 pathway], this pathway is an attractive target for inducing apoptosis in Mtb, this makes it a good drug target. | ||
<StructureSection load='4KXR' size='340' side='right' caption= 'Here shows PE25-PPE41 ligand bound to EspG5 protein. Resolution 2.60Å' scene=''> | |||
==Binding Specificity of EspG5 to PE25-PPE41 Proteins in ''Mycobacterium tuberculosis''== | ==Binding Specificity of EspG5 to PE25-PPE41 Proteins in ''Mycobacterium tuberculosis''== | ||
[[Image:EspG3_White.png|300 px|left|thumb|Figure 1: EspG3 protein (from [http://proteopedia.org/wiki/index.php/4w4i 4w4i])]] | |||
[[Image:EspG3_White.png|300 px|left|thumb|[http://proteopedia.org/wiki/index.php/4w4i | |||
== General Structure and Function == | == General Structure and Function == | ||
The EspG3 protein shown in Figure 1 has a mass of 33.7kD <ref>PMID:25275011</ref>. The proteins beta sheets make up the backbone of the protein (yellow). As a monomeric protein, this binds to its ligand with high specificity. A key beta sheet region on the <scene name='69/694242/Espg3_differences/4'>β-2, β-3</scene> will vary between EspG proteins to influence what the random loop on the PE-PPE protein will interact with. This backbone includes the key residues that interact with the random coil of the ligand. This is surrounded by 8 alpha helices (red) which add to the structure of the protein. One key <scene name='69/694242/Espg3_differences/2'>alpha helix</scene> will vary per EspG protein to stericly limit binding to PE-PPE ligand. The random coil (green) connects the beta sheets and helices together, where the long <scene name='69/694242/Espg3_differences/3'>random loop</scene> variations can impact binding to the EspG's ligand. | |||
Through specific binding factors, an EspG binds to its PE-PPE ligand to be secreted through the ESAT pathway. Though the ESAT-6 secretion system is poorly understood, it is known that PE-PPE proteins and EspG proteins influence virulence and pathogenicity of the infection. | Through specific binding factors, an EspG binds to its PE-PPE ligand to be secreted through the ESAT pathway. Though the ESAT-6 secretion system is poorly understood, it is known that PE-PPE proteins and EspG proteins influence virulence and pathogenicity of the infection. | ||