This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2k2j

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 15:06, 11 September 2015

NMR solution structure of the split PH domain from Phospholipase C gamma 2

Structural highlights

2k2j is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PLCG2 (Homo sapiens)
Activity:	Phosphoinositide phospholipase C, with EC number 3.1.4.11
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[PLCG2_HUMAN] Defects in PLCG2 are the cause of familial cold autoinflammatory syndrome type 3 (FCAS3) [MIM:614468]. An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B cells, defective B cells, increased susceptibility to infection, and increased risk of autoimmune disorders.^[1]

Function

[PLCG2_HUMAN] The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Several isoforms of phospholipase C (PLC) are regulated through interactions with Ras superfamily GTPases, including Rac proteins. Interestingly, of two closely related PLCgamma isoforms, only PLCgamma(2) has previously been shown to be activated by Rac. Here, we explore the molecular basis of this interaction as well as the structural properties of PLCgamma(2) required for activation. Based on reconstitution experiments with isolated PLCgamma variants and Rac2, we show that an unusual pleckstrin homology (PH) domain, designated as the split PH domain (spPH), is both necessary and sufficient to effect activation of PLCgamma(2) by Rac2. We also demonstrate that Rac2 directly binds to PLCgamma(2) as well as to the isolated spPH of this isoform. Furthermore, through the use of NMR spectroscopy and mutational analysis, we determine the structure of spPH, define the structural features of spPH required for Rac interaction, and identify critical amino acid residues at the interaction interface. We further discuss parallels and differences between PLCgamma(1) and PLCgamma(2) and the implications of our findings for their respective signaling roles.

rac regulates its effector phospholipase Cgamma2 through interaction with a split pleckstrin homology domain.,Walliser C, Retlich M, Harris R, Everett KL, Josephs MB, Vatter P, Esposito D, Driscoll PC, Katan M, Gierschik P, Bunney TD J Biol Chem. 2008 Oct 31;283(44):30351-62. Epub 2008 Aug 26. PMID:18728011^[2]

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

References

↑ Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S, Torabi-Parizi P, Subramanian N, Bunney TD, Baxendale RW, Martins MS, Romberg N, Komarow H, Aksentijevich I, Kim HS, Ho J, Cruse G, Jung MY, Gilfillan AM, Metcalfe DD, Nelson C, O'Brien M, Wisch L, Stone K, Douek DC, Gandhi C, Wanderer AA, Lee H, Nelson SF, Shianna KV, Cirulli ET, Goldstein DB, Long EO, Moir S, Meffre E, Holland SM, Kastner DL, Katan M, Hoffman HM, Milner JD. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med. 2012 Jan 26;366(4):330-8. doi: 10.1056/NEJMoa1102140. Epub 2012 Jan, 11. PMID:22236196 doi:10.1056/NEJMoa1102140
↑ Walliser C, Retlich M, Harris R, Everett KL, Josephs MB, Vatter P, Esposito D, Driscoll PC, Katan M, Gierschik P, Bunney TD. rac regulates its effector phospholipase Cgamma2 through interaction with a split pleckstrin homology domain. J Biol Chem. 2008 Oct 31;283(44):30351-62. Epub 2008 Aug 26. PMID:18728011 doi:10.1074/jbc.M803316200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2k2j"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLCG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoinositide_phospholipase_C Phosphoinositide phospholipase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.11 3.1.4.11] </span></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=2k2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k2j RCSB], [http://www.ebi.ac.uk/pdbsum/2k2j PDBsum]</span></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=2k2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k2j OCA], [http://pdbe.org/2k2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k2j RCSB], [http://www.ebi.ac.uk/pdbsum/2k2j PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2k2j" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2k2j

From Proteopedia

Revision as of 15:06, 11 September 2015

NMR solution structure of the split PH domain from Phospholipase C gamma 2

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox