View source for 6axf


==Structure of RasGRP2 in complex with Rap1B==
<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>
</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>
<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>
</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>  
<div style="background-color:#fffaf0;">
== 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<ref>PMID:28952923</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6axf" style="background-color:#fffaf0;"></div>

==See Also==
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Iwig, J S]]
[[Category: Kondo, Y]]
[[Category: Kuriyan, J]]
[[Category: Protein binding]]
[[Category: Signaling protein]]