Vpr protein: Difference between revisions

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== Relevance ==

~~According to~~ 2017, the currently approved anti-HIV drugs target the Pol and Env encoded proteins. These drugs are effective in reducing viral replication. Thus, because of spontaneous mutations that occur during viral replication, drug resistance is evolve<ref>PMID:28681118</ref>. Understanding of Vpr structure and molecular mechanism may facilitate the design of HIV-1 antiviral therapy by its inhibition. Deletion of both ''vpr'' and ''vpx'' genes in SIV, which their protein products in SIV combine Vpr function in HIV-1, eliminate virus replication<ref name='Emerman1996'/>. The multiple significant functions that Vpr fills in HIV-1 replication makes it an attractive candidate for antiviral therapy<ref name='Gonzalez2017'/>.

As of now (October 2017), the currently approved anti-HIV drugs target the Pol and Env encoded proteins. These drugs are effective in reducing viral replication. Thus, because of spontaneous mutations that occur during viral replication, drug resistance is evolve<ref>PMID:28681118</ref>. Understanding of Vpr structure and molecular mechanism may facilitate the design of HIV-1 antiviral therapy by its inhibition. Deletion of both ''vpr'' and ''vpx'' genes in SIV, which their protein products in SIV combine Vpr function in HIV-1, eliminate virus replication<ref name='Emerman1996'/>. The multiple significant functions that Vpr fills in HIV-1 replication makes it an attractive candidate for antiviral therapy<ref name='Gonzalez2017'/>.

== Structural highlights<ref>PMID:12614620</ref> ==

Vpr structure is characterized by three well-defined α-helices: 17–33, 38–50 and 56–77 surrounded by flexible N and C-terminal domains. Vpr ~~have~~ been determined by NMR in the presence of 30% TFE several times, in [[1esx]], [[1vpc]] and [[1ceu]] structures. TFE is known to stabilize secondary structures and to prevent interactions between hydrophobic cores. However, the result was <scene name='75/750237/Vpr/1'>less globular structure</scene> than what it could be in reality. So, another NMR solution of Vpr is determined in the presence 10–30% of CD3CN, a less hydrophobic solvent, and in pure water. <scene name='75/750237/Vpr/2'>In this structure</scene> ([[1m8l]]), the structure folding around a hydrophobic core was improved, and can explain the binding properties of Vpr.

Vpr structure is characterized by three well-defined α-helices: 17–33, 38–50 and 56–77 surrounded by flexible N and C-terminal domains. Vpr has been determined by NMR in the presence of 30% TFE several times, in [[1esx]], [[1vpc]] and [[1ceu]] structures. TFE is known to stabilize secondary structures and to prevent interactions between hydrophobic cores. However, the result was <scene name='75/750237/Vpr/1'>less globular structure</scene> than what it could be in reality. So, another NMR solution of Vpr was determined in the presence 10–30% of CD3CN, a less hydrophobic solvent, and in pure water. <scene name='75/750237/Vpr/2'>In this structure</scene> ([[1m8l]]), the structure folding around a hydrophobic core was improved, and can explain the binding properties of Vpr.

== Conservation ==

Vpr is <scene name='75/750237/Conservation/3'>highly conserved</scene> in HIV and simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates<ref name='Morellet2003'/>. In addition, all primate lentiviruses has Vpr gene whose protein product has highly conserved motifs. HIV-2 and SIVsm lentiviruses have additionally gene - ~~Vpx~~. In these lentiviruses, Vpr and Vpx executes together the roles which HIV-1 Vpr perform. Vpr and Vpx has low conservation between them<ref name='Emerman1996'/>. However, Vpr and Vpx families of proteins use related structural regions to bind and recruit cellular targets to the E3 ligase complex for degradation by the proteasome<ref name='Wu2016'/>.<br/>

Vpr is <scene name='75/750237/Conservation/3'>highly conserved</scene> in HIV and simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates<ref name='Morellet2003'/>. In addition, all primate lentiviruses has Vpr gene whose protein product has highly conserved motifs. HIV-2 and SIVsm lentiviruses have additionally gene - ''vpx''. In these lentiviruses, Vpr and Vpx executes together the roles which HIV-1 Vpr perform. Vpr and Vpx has low conservation between them<ref name='Emerman1996'/>. However, Vpr and Vpx families of proteins use related structural regions to bind and recruit cellular targets to the E3 ligase complex for degradation by the proteasome<ref name='Wu2016'/>.<br/>

[[Image:Consurf_key_small.gif|200px|right]]

Vpr protein: Difference between revisions

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@@ Line 14: / Line 14: @@
 == Relevance ==
-According to 2017, the currently approved anti-HIV drugs target the Pol and Env encoded proteins. These drugs are effective in reducing viral replication. Thus, because of spontaneous mutations that occur during viral replication, drug resistance is evolve<ref>PMID:28681118</ref>. Understanding of Vpr structure and molecular mechanism may facilitate the design of HIV-1 antiviral therapy by its inhibition. Deletion of both ''vpr'' and ''vpx'' genes in SIV, which their protein products in SIV combine Vpr function in HIV-1, eliminate virus replication<ref name='Emerman1996'/>. The multiple significant functions that Vpr fills in HIV-1 replication makes it an attractive candidate for antiviral therapy<ref name='Gonzalez2017'/>.
+As of now (October 2017), the currently approved anti-HIV drugs target the Pol and Env encoded proteins. These drugs are effective in reducing viral replication. Thus, because of spontaneous mutations that occur during viral replication, drug resistance is evolve<ref>PMID:28681118</ref>. Understanding of Vpr structure and molecular mechanism may facilitate the design of HIV-1 antiviral therapy by its inhibition. Deletion of both ''vpr'' and ''vpx'' genes in SIV, which their protein products in SIV combine Vpr function in HIV-1, eliminate virus replication<ref name='Emerman1996'/>. The multiple significant functions that Vpr fills in HIV-1 replication makes it an attractive candidate for antiviral therapy<ref name='Gonzalez2017'/>.
 == Structural highlights<ref>PMID:12614620</ref> ==
-Vpr structure is characterized by three well-defined α-helices: 17–33, 38–50 and 56–77 surrounded by flexible N and C-terminal domains. Vpr have been determined by NMR in the presence of 30% TFE several times, in [[1esx]], [[1vpc]] and [[1ceu]] structures. TFE is known to stabilize secondary structures and to prevent interactions between hydrophobic cores. However, the result was <scene name='75/750237/Vpr/1'>less globular structure</scene> than what it could be in reality. So, another NMR solution of Vpr is determined in the presence 10–30% of CD3CN, a less hydrophobic solvent, and in pure water. <scene name='75/750237/Vpr/2'>In this structure</scene> ([[1m8l]]), the structure folding around a hydrophobic core was improved, and can explain the binding properties of Vpr.
+Vpr structure is characterized by three well-defined α-helices: 17–33, 38–50 and 56–77 surrounded by flexible N and C-terminal domains. Vpr has been determined by NMR in the presence of 30% TFE several times, in [[1esx]], [[1vpc]] and [[1ceu]] structures. TFE is known to stabilize secondary structures and to prevent interactions between hydrophobic cores. However, the result was <scene name='75/750237/Vpr/1'>less globular structure</scene> than what it could be in reality. So, another NMR solution of Vpr was determined in the presence 10–30% of CD3CN, a less hydrophobic solvent, and in pure water. <scene name='75/750237/Vpr/2'>In this structure</scene> ([[1m8l]]), the structure folding around a hydrophobic core was improved, and can explain the binding properties of Vpr.
 == Conservation ==
-Vpr is <scene name='75/750237/Conservation/3'>highly conserved</scene> in HIV and  simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates<ref name='Morellet2003'/>. In addition, all primate lentiviruses has Vpr gene whose protein product has highly conserved motifs. HIV-2 and SIVsm lentiviruses have additionally gene - Vpx. In these lentiviruses, Vpr and Vpx executes together the roles which HIV-1 Vpr perform. Vpr and Vpx has low conservation between them<ref name='Emerman1996'/>. However, Vpr and Vpx families of proteins use related structural regions to bind and recruit cellular targets to the E3 ligase complex for degradation by the proteasome<ref name='Wu2016'/>.<br/>
+Vpr is <scene name='75/750237/Conservation/3'>highly conserved</scene> in HIV and  simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates<ref name='Morellet2003'/>. In addition, all primate lentiviruses has Vpr gene whose protein product has highly conserved motifs. HIV-2 and SIVsm lentiviruses have additionally gene - ''vpx''. In these lentiviruses, Vpr and Vpx executes together the roles which HIV-1 Vpr perform. Vpr and Vpx has low conservation between them<ref name='Emerman1996'/>. However, Vpr and Vpx families of proteins use related structural regions to bind and recruit cellular targets to the E3 ligase complex for degradation by the proteasome<ref name='Wu2016'/>.<br/>
 [[Image:Consurf_key_small.gif|200px|right]]