6axf

From Proteopedia

(Difference between revisions)

Current revision

Structure of RasGRP2 in complex with Rap1B

Structural highlights

6axf is a 16 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 3.1Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GRP2_HUMAN Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to that of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. The transition from the autoinhibited to the active form of RasGRP1 involves the rearrangement of an inter-domain linker that displaces inhibitory inter-domain interactions. His 212 is located at the fulcrum of these conformational changes, and structural features in its vicinity are consistent with its function as a pH-dependent switch.

A histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.,Vercoulen Y, Kondo Y, Iwig JS, Janssen A, White KA, Amini M, Barber DL, Kuriyan J, Roose JP Elife. 2017 Sep 27;6. pii: e29002. doi: 10.7554/eLife.29002. PMID:28952923^[5]

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

References

↑ Clyde-Smith J, Silins G, Gartside M, Grimmond S, Etheridge M, Apolloni A, Hayward N, Hancock JF. Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor. J Biol Chem. 2000 Oct 13;275(41):32260-7. PMID:10918068 doi:10.1074/jbc.M006087200
↑ Katagiri K, Shimonaka M, Kinashi T. Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1. J Biol Chem. 2004 Mar 19;279(12):11875-81. Epub 2003 Dec 31. PMID:14702343 doi:10.1074/jbc.M310717200
↑ Ghandour H, Cullere X, Alvarez A, Luscinskas FW, Mayadas TN. Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion. Blood. 2007 Nov 15;110(10):3682-90. Epub 2007 Aug 16. PMID:17702895 doi:blood-2007-03-077628
↑ Pasvolsky R, Feigelson SW, Kilic SS, Simon AJ, Tal-Lapidot G, Grabovsky V, Crittenden JR, Amariglio N, Safran M, Graybiel AM, Rechavi G, Ben-Dor S, Etzioni A, Alon R. A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets. J Exp Med. 2007 Jul 9;204(7):1571-82. Epub 2007 Jun 18. PMID:17576779 doi:10.1084/jem.20070058
↑ Vercoulen Y, Kondo Y, Iwig JS, Janssen A, White KA, Amini M, Barber DL, Kuriyan J, Roose JP. A histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1. Elife. 2017 Sep 27;6. pii: e29002. doi: 10.7554/eLife.29002. PMID:28952923 doi:http://dx.doi.org/10.7554/eLife.29002

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6axf"

Categories: Homo sapiens | Large Structures | Iwig JS | Kondo Y | Kuriyan J

@@ Line 3: / Line 3: @@
 <StructureSection load='6axf' size='340' side='right'caption='[[6axf]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6axf]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AXF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6AXF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6axf]] is a 16 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=6AXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AXF FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 3.1&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6axf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axf OCA], [http://pdbe.org/6axf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6axf RCSB], [http://www.ebi.ac.uk/pdbsum/6axf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6axf ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=6axf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6axf OCA], [https://pdbe.org/6axf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6axf RCSB], [https://www.ebi.ac.uk/pdbsum/6axf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6axf ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GRP2_HUMAN GRP2_HUMAN]] Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.<ref>PMID:10918068</ref> <ref>PMID:14702343</ref> <ref>PMID:17702895</ref> <ref>PMID:17576779</ref>  [[http://www.uniprot.org/uniprot/RAP1B_HUMAN RAP1B_HUMAN]] GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction.<ref>PMID:20332120</ref> <ref>PMID:18660803</ref>
+[https://www.uniprot.org/uniprot/GRP2_HUMAN GRP2_HUMAN] Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.<ref>PMID:10918068</ref> <ref>PMID:14702343</ref> <ref>PMID:17702895</ref> <ref>PMID:17576779</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Iwig, J S]]
+[[Category: Iwig JS]]
-[[Category: Kondo, Y]]
+[[Category: Kondo Y]]
-[[Category: Kuriyan, J]]
+[[Category: Kuriyan J]]
-[[Category: Protein binding]]
-[[Category: Signaling protein]]

6axf

From Proteopedia

Current revision

Structure of RasGRP2 in complex with Rap1B

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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