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5xhz

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Revision as of 05:55, 25 April 2018

Crystal Structure Analysis of CIN85-SH3B in complex with ARAP1-P2

Structural highlights

5xhz is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Sh3kbp1, Ruk, Seta (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SH3K1_MOUSE] Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through a association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit. May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration (By similarity). [ARAP1_MOUSE] 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. Has a preference for ARF1 and ARF5 (By similarity).

Publication Abstract from PubMed

Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1), Cbl-interacting protein of 85 kDa (CIN85), and casitas B-lineage lymphoma (Cbl) play important roles in epidermal growth factor receptor (EGFR) internalization and recycling. In previous studies, ARAP1 was found to interact with CIN85, and their interaction attenuated the ubiquitination of EGFR. However, the molecular mechanism was still unclear. In this study, we first biochemically and structurally characterized the interaction between ARAP1 and CIN85, and found that the CIN85 SH3B domain bound to the ARAP1 PXPXXRX (except P) XXR/H/K motif with high affinity and specificity. Based on this binding model, we further predicted other potential CIN85 binding partners and tested their interactions biochemically. Moreover, our swapping data and structure alignment analysis suggested that the beta2-beta3 loops of the CIN85 SH3 domains and the H87ARAP1/E132CIN85 interaction were critical for ARAP1 binding specificity. Finally, our competitive analytical gel-filtration chromatography and isothermal titration calorimetry (ITC) results showed that ARAP1 could compete with Cbl for CIN85 binding, which provides a biochemical basis for the regulatory roles of ARAP1 in the CIN85-mediated EGFR internalizing process.

Biochemical and Structural Studies of the Interaction between ARAP1 and CIN85.,Li Q, Yang W, Wang Y, Liu W Biochemistry. 2018 Apr 10;57(14):2132-2139. doi: 10.1021/acs.biochem.8b00057., Epub 2018 Mar 28. PMID:29589748^[1]

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

References

↑ Li Q, Yang W, Wang Y, Liu W. Biochemical and Structural Studies of the Interaction between ARAP1 and CIN85. Biochemistry. 2018 Apr 10;57(14):2132-2139. doi: 10.1021/acs.biochem.8b00057., Epub 2018 Mar 28. PMID:29589748 doi:http://dx.doi.org/10.1021/acs.biochem.8b00057

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/5xhz"

Categories: Lk3 transgenic mice | Liu, W | Yang, W | Protein binding | Protein-protein complex

@@ Line 3: / Line 3: @@
 <StructureSection load='5xhz' size='340' side='right' caption='[[5xhz]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xhz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XHZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xhz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XHZ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sh3kbp1, Ruk, Seta ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5xhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xhz OCA], [http://pdbe.org/5xhz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xhz RCSB], [http://www.ebi.ac.uk/pdbsum/5xhz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xhz ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Lk3 transgenic mice]]
 [[Category: Liu, W]]
 [[Category: Yang, W]]
 [[Category: Protein binding]]
 [[Category: Protein-protein complex]]

5xhz

From Proteopedia

Revision as of 05:55, 25 April 2018

Crystal Structure Analysis of CIN85-SH3B in complex with ARAP1-P2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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