User:Olivier Laprevote/Sandbox 1

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 19: Line 19:
The Vav1 <scene name='75/751211/Structure_vav/3'>structural domains</scene> are (from N ter to C ter): a '''calponin-homology''' (CH) domain, an '''acidic''' (Ac) domain, a '''DBL-homology''' (DH) domain also known as a '''rhoGEF''' domain, a '''pleckstrin-homology''' (PH) domain, a '''phorbol esters/diacylglycerol binding''' (C1) domain also called Zinc-finger domain and '''Src-homology''' (SH) 3 and 2 domains. <ref>http://smart.embl.de/smart/show_motifs.pl?GENOMIC=1&DO_PFAM=DO_PFAM&INCLUDE_SIGNALP=INCLUDE_SIGNALP&ID=9606.ENSP00000472929</ref> <ref>PMID:20141838 </ref>
The Vav1 <scene name='75/751211/Structure_vav/3'>structural domains</scene> are (from N ter to C ter): a '''calponin-homology''' (CH) domain, an '''acidic''' (Ac) domain, a '''DBL-homology''' (DH) domain also known as a '''rhoGEF''' domain, a '''pleckstrin-homology''' (PH) domain, a '''phorbol esters/diacylglycerol binding''' (C1) domain also called Zinc-finger domain and '''Src-homology''' (SH) 3 and 2 domains. <ref>http://smart.embl.de/smart/show_motifs.pl?GENOMIC=1&DO_PFAM=DO_PFAM&INCLUDE_SIGNALP=INCLUDE_SIGNALP&ID=9606.ENSP00000472929</ref> <ref>PMID:20141838 </ref>
-
<scene name='75/751211/Ch_domain/1'>Calponin-homology (CH) domain</scene> (residues 1 - 119): When the CH domain is deleted, Vav has a phosphorylation-independant GEF activity. Studies on Vav3 implies that CH plays a role in inhibition via its interactions with the <scene name='75/751211/Ch_and_ac/1'>Ac</scene> (between the residue 49 in CH and 181 in Ac), DH and <scene name='75/751211/Ch_and_c1/1'>C1</scene> regions (C1 interacts with L101 and L104 of CH). The contacts with DH and C1 seem passively driven by the interactions between Ac and CH, though. <ref>PMID:15775967</ref>
+
<scene name='75/751211/Ch_domain/1'>Calponin-homology (CH) domain</scene> (residues 1 - 119): When the CH domain is deleted, Vav has a phosphorylation-independant GEF activity. Studies on Vav3 implies that CH plays a role in '''auto-inhibition''' of Vav via its interactions with the <scene name='75/751211/Ch_and_ac/1'>Ac</scene> (between the residue 49 in CH and 181 in Ac), DH and <scene name='75/751211/Ch_and_c1/1'>C1</scene> regions (C1 interacts with L101 and L104 of CH). The contacts with DH and C1 seem '''passively driven''' by the interactions between Ac and CH, though. <ref>PMID:15775967</ref>
-
<scene name='75/751211/Ac_domain/1'>Acidic (Ac) domain</scene> (residues 134 - 187): contains the Tyrosine (Y174) which activates Vav activity when phosphorylated. <ref>PMID:20141838 </ref>
+
<scene name='75/751211/Ac_domain/1'>Acidic (Ac) domain</scene> (residues 134 - 187): contains the Tyrosine (Y174) which '''activates Vav''' when phosphorylated. <ref>PMID:20141838 </ref>
-
<scene name='75/751211/Dh_domain/1'>DBL-homology (DH) domain</scene> (residues 194 - 373): present in every Rho/rac GEF, it is the active site of the GTP exchange with the C1 domain in Vav. It always has a PH domain just after its C terminal.<ref>http://pfam.xfam.org/family/PF00621</ref>
+
<scene name='75/751211/Dh_domain/1'>DBL-homology (DH) domain</scene> (residues 194 - 373): present in every Rho/rac GEF, it is the '''active site''' of the GTP exchange with the C1 domain in Vav. It always has a PH domain just after its C terminal.<ref>http://pfam.xfam.org/family/PF00621</ref>
-
Pleckstrin-homology (PH) domain (residues 402 - 504): point mutation in it don't change the exchange activity of Vav, so it isn't directly involved in its GEF function <ref>PMID: 10523675 </ref>. But the presence of phosphatidylinositol-4,5-bisphosphate (PIP 2) inhibates 90% of Vav activity while phosphatidylinositol-3,4,5-trisphosphate doubles it. It is very likely that the interactions between these lipids and Vav happen on the PH domain, as it is commonly the case on other proteins with this domain. It should be noted that the activation of Vav is made in parallel of the one of PI3-kinase in TCR and BCR pathway. <ref>PMID: 9438848</ref>
+
<scene name='75/751211/Ph_domain/1'>Pleckstrin-homology (PH) domain</scene> (residues 402 - 504): point mutation in it don't change the exchange activity of Vav, so it '''isn't directly involved''' in its GEF function <ref>PMID: 10523675 </ref>. But the presence of '''phosphatidylinositol-4,5-bisphosphate''' (PIP 2) inhibits 90% of Vav activity while '''phosphatidylinositol-3,4,5-trisphosphate''' doubles it. It is very likely that the interactions between these lipids and Vav happen on the PH domain, as it is commonly the case on other proteins with this region. It should be noted that the activation of Vav is made in parallel of the one of '''PI3-kinase''' in TCR and BCR pathway. <ref>PMID: 9438848</ref>
-
 
+
phorbol esters/diacylglycerol binding (C1) domain :
-
 
+
-
phorbol esters/diacylglycerol binding (C1) domain
+

Revision as of 13:14, 27 January 2017

Proto-oncogene vav

Caption for this structure

Drag the structure with the mouse to rotate

References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ http://www.uniprot.org/uniprot/P15498#function
  4. ↑ http://smart.embl.de/smart/show_motifs.pl?GENOMIC=1&DO_PFAM=DO_PFAM&INCLUDE_SIGNALP=INCLUDE_SIGNALP&ID=9606.ENSP00000472929
  5. ↑ Yu B, Martins IR, Li P, Amarasinghe GK, Umetani J, Fernandez-Zapico ME, Billadeau DD, Machius M, Tomchick DR, Rosen MK. Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1. Cell. 2010 Jan 22;140(2):246-56. PMID:20141838 doi:10.1016/j.cell.2009.12.033
  6. ↑ Llorca O, Arias-Palomo E, Zugaza JL, Bustelo XR. Global conformational rearrangements during the activation of the GDP/GTP exchange factor Vav3. EMBO J. 2005 Apr 6;24(7):1330-40. Epub 2005 Mar 10. PMID:15775967 doi:http://dx.doi.org/10.1038/sj.emboj.7600617
  7. ↑ Yu B, Martins IR, Li P, Amarasinghe GK, Umetani J, Fernandez-Zapico ME, Billadeau DD, Machius M, Tomchick DR, Rosen MK. Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1. Cell. 2010 Jan 22;140(2):246-56. PMID:20141838 doi:10.1016/j.cell.2009.12.033
  8. ↑ http://pfam.xfam.org/family/PF00621
  9. ↑ Movilla N, Bustelo XR. Biological and regulatory properties of Vav-3, a new member of the Vav family of oncoproteins. Mol Cell Biol. 1999 Nov;19(11):7870-85. PMID:10523675
  10. ↑ Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD, Krishna UM, Falck JR, White MA, Broek D. Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science. 1998 Jan 23;279(5350):558-60. PMID:9438848

Proteopedia Page Contributors and Editors (what is this?)

Olivier Laprevote

Retrieved from "http://52.214.119.220/wiki/index.php/User:Olivier_Laprevote/Sandbox_1"
Personal tools