7kk7

crystal structure of ligand-free PLEKHA7 PH domaincrystal structure of ligand-free PLEKHA7 PH domain

Structural highlights

7kk7 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 2.8Å
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

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OCA

[1] 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

[2] 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

[3] 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

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7kk7

crystal structure of ligand-free PLEKHA7 PH domaincrystal structure of ligand-free PLEKHA7 PH domain

Structural highlights

Function

Publication Abstract from PubMed

References

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7kk7

crystal structure of ligand-free PLEKHA7 PH domaincrystal structure of ligand-free PLEKHA7 PH domain

Structural highlights

Function

Publication Abstract from PubMed

References

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