7kjz

From Proteopedia

(Difference between revisions)

Current revision

crystal structure of PLEKHA7 PH domain biding inositol-tetraphosphate

Structural highlights

7kjz is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.43Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PKHA7_HUMAN Required for zonula adherens biogenesis and maintenance (PubMed:19041755). Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site (PubMed:19041755). Mediates docking of ADAM10 to zonula adherens through a PDZD11-dependent interaction with the ADAM10-binding protein TSPAN33 (PubMed:30463011).^[1] ^[2]

Publication Abstract from PubMed

PLEKHA7 (pleckstrin homology domain containing family A member 7) plays key roles in intracellular signaling, cytoskeletal organization, and cell adhesion, and is associated with multiple human cancers. The interactions of its pleckstrin homology (PH) domain with membrane phosphatidyl-inositol-phosphate (PIP) lipids are critical for proper cellular localization and function, but little is known about how PLEKHA7 and other PH domains interact with membrane-embedded PIPs. Here we describe the structural basis for recognition of membrane-bound PIPs by PLEHA7. Using X-ray crystallography, nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the interaction of PLEKHA7 with PIPs is multivalent, distinct from a discrete one-to-one interaction, and induces PIP clustering. Our findings reveal a central role of the membrane assembly in mediating protein-PIP association and provide a roadmap for understanding how the PH domain contributes to the signaling, adhesion, and nanoclustering functions of PLEKHA7.

Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids.,Aleshin AE, Yao Y, Iftikhar A, Bobkov AA, Yu J, Cadwell G, Klein MG, Dong C, Bankston LA, Liddington RC, Im W, Powis G, Marassi FM Structure. 2021 Apr 13. pii: S0969-2126(21)00116-7. doi:, 10.1016/j.str.2021.03.018. PMID:33878292^[3]

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

References

↑ Meng W, Mushika Y, Ichii T, Takeichi M. Anchorage of microtubule minus ends to adherens junctions regulates epithelial cell-cell contacts. Cell. 2008 Nov 28;135(5):948-59. doi: 10.1016/j.cell.2008.09.040. PMID:19041755 doi:http://dx.doi.org/10.1016/j.cell.2008.09.040
↑ Shah J, Rouaud F, Guerrera D, Vasileva E, Popov LM, Kelley WL, Rubinstein E, Carette JE, Amieva MR, Citi S. A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote alpha-Toxin Cytotoxicity. Cell Rep. 2018 Nov 20;25(8):2132-2147.e7. doi: 10.1016/j.celrep.2018.10.088. PMID:30463011 doi:http://dx.doi.org/10.1016/j.celrep.2018.10.088
↑ Aleshin AE, Yao Y, Iftikhar A, Bobkov AA, Yu J, Cadwell G, Klein MG, Dong C, Bankston LA, Liddington RC, Im W, Powis G, Marassi FM. Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids. Structure. 2021 Apr 13. pii: S0969-2126(21)00116-7. doi:, 10.1016/j.str.2021.03.018. PMID:33878292 doi:http://dx.doi.org/10.1016/j.str.2021.03.018

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7kjz"

Categories: Homo sapiens | Large Structures | Aleshin AE | Liddington RC | Marassi FM

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7kjz is ON HOLD  until Paper Publication
+==crystal structure of PLEKHA7 PH domain biding inositol-tetraphosphate==
+<StructureSection load='7kjz' size='340' side='right'caption='[[7kjz]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7kjz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KJZ FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.43&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7kjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kjz OCA], [https://pdbe.org/7kjz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kjz RCSB], [https://www.ebi.ac.uk/pdbsum/7kjz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kjz ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PKHA7_HUMAN PKHA7_HUMAN] Required for zonula adherens biogenesis and maintenance (PubMed:19041755). Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site (PubMed:19041755). Mediates docking of ADAM10 to zonula adherens through a PDZD11-dependent interaction with the ADAM10-binding protein TSPAN33 (PubMed:30463011).<ref>PMID:19041755</ref> <ref>PMID:30463011</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+PLEKHA7 (pleckstrin homology domain containing family A member 7) plays key roles in intracellular signaling, cytoskeletal organization, and cell adhesion, and is associated with multiple human cancers. The interactions of its pleckstrin homology (PH) domain with membrane phosphatidyl-inositol-phosphate (PIP) lipids are critical for proper cellular localization and function, but little is known about how PLEKHA7 and other PH domains interact with membrane-embedded PIPs. Here we describe the structural basis for recognition of membrane-bound PIPs by PLEHA7. Using X-ray crystallography, nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the interaction of PLEKHA7 with PIPs is multivalent, distinct from a discrete one-to-one interaction, and induces PIP clustering. Our findings reveal a central role of the membrane assembly in mediating protein-PIP association and provide a roadmap for understanding how the PH domain contributes to the signaling, adhesion, and nanoclustering functions of PLEKHA7.
-Authors: Marassi, F.M., Aleshin, A.E., Liddington, R.C.
+Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids.,Aleshin AE, Yao Y, Iftikhar A, Bobkov AA, Yu J, Cadwell G, Klein MG, Dong C, Bankston LA, Liddington RC, Im W, Powis G, Marassi FM Structure. 2021 Apr 13. pii: S0969-2126(21)00116-7. doi:, 10.1016/j.str.2021.03.018. PMID:33878292<ref>PMID:33878292</ref>
-Description: crystal structure of PLEKHA7 PH domain biding inositol-tetraphosphate
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Marassi, F.M]]
+<div class="pdbe-citations 7kjz" style="background-color:#fffaf0;"></div>
-[[Category: Liddington, R.C]]
+== References ==
-[[Category: Aleshin, A.E]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Aleshin AE]]
+[[Category: Liddington RC]]
+[[Category: Marassi FM]]

7kjz

From Proteopedia

Current revision

crystal structure of PLEKHA7 PH domain biding inositol-tetraphosphate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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