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7yir

From Proteopedia

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Current revision

Crystal structure of N-terminal PH domain of ARAP3 protein from human

Structural highlights

7yir is a 1 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 2.099Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ARAP3_HUMAN Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.^[1] ^[2]

Publication Abstract from PubMed

Arap3, a dual GTPase-activating protein (GAP) for the small GTPases Arf6 and RhoA, plays key roles in regulating a wide range of biological processes, including cancer cell invasion and metastasis. It is known that Arap3 is a PI3K effector that can bind directly to PI(3,4,5)P3, and the PI(3,4,5)P3-mediated plasma membrane recruitment is crucial for its function. However, the molecular mechanism of how the protein recognizes PI(3,4,5)P3 remains unclear. Here, using liposome pull-down and surface plasmon resonance (SPR) analysis, we found that the N-terminal first pleckstrin homology (PH) domain (Arap3-PH1) can interact with PI(3,4,5)P3 and, with lower affinity, with PI(4,5)P2. To understand how Arap3-PH1 and phosphoinositide (PIP) lipids interact, we solved the crystal structure of the Arap3-PH1 in the apo form and complex with diC4-PI(3,4,5)P3. We also characterized the interactions of Arap3-PH1 with diC4-PI(3,4,5)P3 and diC4-PI(4,5)P2 in solution by nuclear magnetic resonance (NMR) spectroscopy. Furthermore, we found overexpression of Arap3 could inhibit breast cancer cell invasion in vitro, and the PIPs-binding ability of the PH1 domain is essential for this function.

Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3.,Zhang Y, Ge L, Xu L, Liu Y, Wang J, Liu C, Zhao H, Xing L, Wang J, Wu B Int J Mol Sci. 2023 Jan 6;24(2):1125. doi: 10.3390/ijms24021125. PMID:36674645^[3]

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

References

↑ Krugmann S, Anderson KE, Ridley SH, Risso N, McGregor A, Coadwell J, Davidson K, Eguinoa A, Ellson CD, Lipp P, Manifava M, Ktistakis N, Painter G, Thuring JW, Cooper MA, Lim ZY, Holmes AB, Dove SK, Michell RH, Grewal A, Nazarian A, Erdjument-Bromage H, Tempst P, Stephens LR, Hawkins PT. Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices. Mol Cell. 2002 Jan;9(1):95-108. PMID:11804589
↑ Lu Q, Wei W, Kowalski PE, Chang AC, Cohen SN. EST-based genome-wide gene inactivation identifies ARAP3 as a host protein affecting cellular susceptibility to anthrax toxin. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17246-51. Epub 2004 Nov 29. PMID:15569923 doi:http://dx.doi.org/10.1073/pnas.0407794101
↑ Zhang Y, Ge L, Xu L, Liu Y, Wang J, Liu C, Zhao H, Xing L, Wang J, Wu B. Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3. Int J Mol Sci. 2023 Jan 6;24(2):1125. PMID:36674645 doi:10.3390/ijms24021125

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/7yir"

Categories: Homo sapiens | Large Structures | Liu YR | Wu B | Zhang YJ

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7yir]] is a 1 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=7YIR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YIR FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.099&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=7yir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yir OCA], [https://pdbe.org/7yir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yir RCSB], [https://www.ebi.ac.uk/pdbsum/7yir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yir ProSAT]</span></td></tr>
 </table>

7yir

From Proteopedia

Current revision

Crystal structure of N-terminal PH domain of ARAP3 protein from human

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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