2koh

From Proteopedia

(Difference between revisions)

Revision as of 20:58, 24 December 2014

NMR structure of mouse Par3-PDZ3 in complex with VE-Cadherin C-terminus

Structural highlights

2koh is a 2 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Par3, Pard3 (Mus musculus), Cdh5, VE-Cadherin (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PARD3_MOUSE] Adapter protein involved in asymmetrical cell division and cell polarization processes. Seems to play a central role in the formation of epithelial tight junctions. Targets the phosphatase PTEN to cell junctions. Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Involved in Schwann cell peripheral myelination. [CADH5_MOUSE] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. This cadherin may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. Acts in concert with KRIT1 to establish and maintain correct endothelial cell polarity and vascular lumen. These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for activation of PRKCZ and for localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

par3 is a multiple-PDZ-containing scaffold protein that is central to the organization of an evolutionarily conserved cell polarity complex consisting of par3, par6, and aPKC. The ability of par3 PDZ domains to target various adhesion molecules and enzymes at the plasma membrane leads to the controlled localization of par6 and aPKC, which has firmly established its role in epithelial cell polarity. Of the numerous PDZ ligands associated with par3, interaction of its third PDZ domain with the class II ligand found within the C-terminal tail of vascular endothelial cadherin (VE-Cad) suggests a role in endothelial cell polarity as well, but the molecular details of the interaction are unknown. Previously determined structures of par3-PDZ3 bound to the class I ligand found within the C-terminal tail of the phosphoinositide phosphatase PTEN revealed two discrete binding sites: a canonical PDZ-ligand interaction site and a distal site involving charge-charge complements. Currently, it is unclear if par3-PDZ3 employs both canonical and distal binding modes in its association with VE-Cad or if these modes are unique to the PTEN interaction, suggesting a possible mechanism for ligand specificity within the polarity network. The structure of par3-PDZ3 bound to the C-terminal tail of VE-Cad presented in this work shows that both canonical and distal interactions are utilized in binding. Biophysical measurements using fluorescence polarization and two-dimensional NMR implicate the intermolecular charge pairing of aspartic acid 777 (VE-Cad) and arginine 609 (par3-PDZ3) as a crucial modulator of complex formation. Phosphorylation of VE-Cad at serine 776 increases its affinity for par3, demonstrating that post-translational modifications outside of the canonical carboxylate binding site can enhance PDZ-ligand interactions. Comparison of the VE-Cad and PTEN complexes highlights how the unique molecular architecture of par3-PDZ3 can accommodate both canonical and distal interaction modes that allow dual-class specificity for these two ligand types.

Distal interactions within the par3-VE-cadherin complex.,Tyler RC, Peterson FC, Volkman BF Biochemistry. 2010 Feb 9;49(5):951-7. PMID:20047332^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Matsuyoshi N, Toda K, Horiguchi Y, Tanaka T, Nakagawa S, Takeichi M, Imamura S. In vivo evidence of the critical role of cadherin-5 in murine vascular integrity. Proc Assoc Am Physicians. 1997 Jul;109(4):362-71. PMID:9220534
↑ Lampugnani MG, Orsenigo F, Rudini N, Maddaluno L, Boulday G, Chapon F, Dejana E. CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci. 2010 Apr 1;123(Pt 7):1073-80. doi: 10.1242/jcs.059329. PMID:20332120 doi:10.1242/jcs.059329
↑ Tyler RC, Peterson FC, Volkman BF. Distal interactions within the par3-VE-cadherin complex. Biochemistry. 2010 Feb 9;49(5):951-7. PMID:20047332 doi:10.1021/bi9017335

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2koh"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2koh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KOH FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Par3, Pard3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Cdh5, VE-Cadherin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Par3, Pard3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Cdh5, VE-Cadherin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2koh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2koh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2koh RCSB], [http://www.ebi.ac.uk/pdbsum/2koh PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2koh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2koh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2koh RCSB], [http://www.ebi.ac.uk/pdbsum/2koh PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PARD3_MOUSE PARD3_MOUSE]] Adapter protein involved in asymmetrical cell division and cell polarization processes. Seems to play a central role in the formation of epithelial tight junctions. Targets the phosphatase PTEN to cell junctions. Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Involved in Schwann cell peripheral myelination. [[http://www.uniprot.org/uniprot/CADH5_MOUSE CADH5_MOUSE]] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. This cadherin may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. Acts in concert with KRIT1 to establish and maintain correct endothelial cell polarity and vascular lumen. These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for activation of PRKCZ and for localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction.<ref>PMID:9220534</ref> <ref>PMID:20332120</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 34: @@
 </StructureSection>
 [[Category: Mus musculus]]
-[[Category: Peterson, F C.]]
+[[Category: Peterson, F C]]
-[[Category: Tyler, R C.]]
+[[Category: Tyler, R C]]
-[[Category: Volkman, B F.]]
+[[Category: Volkman, B F]]
 [[Category: Cell adhesion]]
 [[Category: Cell cycle]]

2koh

From Proteopedia

Revision as of 20:58, 24 December 2014

NMR structure of mouse Par3-PDZ3 in complex with VE-Cadherin C-terminus

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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