8jqh

From Proteopedia

(Difference between revisions)

Current revision

Cryo EM map of full length PLC gamma 2 in autoinhibition state

Structural highlights

8jqh 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:	Electron Microscopy, Resolution 4.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

Publication Abstract from PubMed

Phospholipase C gamma 2 (PLCgamma2) plays important roles in cell signaling downstream of various membrane receptors. PLCgamma2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCgamma2 activity modulation. Here we determined three structures of human PLCgamma2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the Src homology 3 (SH3) domain in the inhibitory region, and its previously unknown interaction with a carboxyl-terminal helical domain in the core region. We also determined a structure of PLCgamma2 bound to the kinase domain of fibroblast growth factor receptor 1 (FGFR1), which demonstrates the recognition of FGFR1 by the nSH2 domain in the inhibitory region of PLCgamma2. Our results provide structural insights into PLCgamma2 regulation that will facilitate future mechanistic studies to understand the entire activation process.

The crystal and cryo-EM structures of PLCgamma2 reveal dynamic interdomain recognitions in autoinhibition.,Shin YC, Plummer-Medeiros AM, Mungenast A, Choi HW, TenDyke K, Zhu X, Shepard J, Sanders K, Zhuang N, Hu L, Qian D, Song K, Xu C, Wang J, Poda SB, Liao M, Chen Y Sci Adv. 2024 Nov 29;10(48):eadn6037. doi: 10.1126/sciadv.adn6037. Epub 2024 Nov , 29. PMID:39612343^[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
↑ Shin YC, Plummer-Medeiros AM, Mungenast A, Choi HW, TenDyke K, Zhu X, Shepard J, Sanders K, Zhuang N, Hu L, Qian D, Song K, Xu C, Wang J, Poda SB, Liao M, Chen Y. The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition. Sci Adv. 2024 Nov 29;10(48):eadn6037. PMID:39612343 doi:10.1126/sciadv.adn6037

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8jqh"

Categories: Homo sapiens | Large Structures | Liao M | Shin Y-C

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8jqh is ON HOLD
+==Cryo EM map of full length PLC gamma 2 in autoinhibition state==
+<StructureSection load='8jqh' size='340' side='right'caption='[[8jqh]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jqh]] 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=8JQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JQH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2&#8491;</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=8jqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jqh OCA], [https://pdbe.org/8jqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jqh RCSB], [https://www.ebi.ac.uk/pdbsum/8jqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jqh ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PLCG2_HUMAN PLCG2_HUMAN] Defects in PLCG2 are the cause of familial cold autoinflammatory syndrome type 3 (FCAS3) [MIM:[https://omim.org/entry/614468 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.<ref>PMID:22236196</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PLCG2_HUMAN 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Phospholipase C gamma 2 (PLCgamma2) plays important roles in cell signaling downstream of various membrane receptors. PLCgamma2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCgamma2 activity modulation. Here we determined three structures of human PLCgamma2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the Src homology 3 (SH3) domain in the inhibitory region, and its previously unknown interaction with a carboxyl-terminal helical domain in the core region. We also determined a structure of PLCgamma2 bound to the kinase domain of fibroblast growth factor receptor 1 (FGFR1), which demonstrates the recognition of FGFR1 by the nSH2 domain in the inhibitory region of PLCgamma2. Our results provide structural insights into PLCgamma2 regulation that will facilitate future mechanistic studies to understand the entire activation process.
-Authors:
+The crystal and cryo-EM structures of PLCgamma2 reveal dynamic interdomain recognitions in autoinhibition.,Shin YC, Plummer-Medeiros AM, Mungenast A, Choi HW, TenDyke K, Zhu X, Shepard J, Sanders K, Zhuang N, Hu L, Qian D, Song K, Xu C, Wang J, Poda SB, Liao M, Chen Y Sci Adv. 2024 Nov 29;10(48):eadn6037. doi: 10.1126/sciadv.adn6037. Epub 2024 Nov , 29. PMID:39612343<ref>PMID:39612343</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8jqh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Liao M]]
+[[Category: Shin Y-C]]

8jqh

From Proteopedia

Current revision

Cryo EM map of full length PLC gamma 2 in autoinhibition state

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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