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TitleThe crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition.
Journal, issue, pagesSci Adv, Vol. 10, Issue 48, Page eadn6037, Year 2024
Publish dateNov 29, 2024
AuthorsYoung-Cheul Shin / Ashlee Marie Plummer-Medeiros / Alison Mungenast / Hyeong-Wook Choi / Karen TenDyke / Xiaojie Zhu / Jennifer Shepard / Kristen Sanders / Ningning Zhuang / Liang Hu / Dongming Qian / Kangkang Song / Chen Xu / John Wang / Suresh B Poda / Maofu Liao / Yu Chen /
PubMed AbstractPhospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while ...Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 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 PLCγ2 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 PLCγ2. Our results provide structural insights into PLCγ2 regulation that will facilitate future mechanistic studies to understand the entire activation process.
External linksSci Adv / PubMed:39612343 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.55 - 4.2 Å
Structure data

36571

8jqg

EMDB-36571, PDB-8jqg:
Cryo EM map of full length PLC gamma 2
Method: EM (single particle) / Resolution: 3.72 Å

36572

8jqh

EMDB-36572, PDB-8jqh:
Cryo EM map of full length PLC gamma 2 in autoinhibition state
Method: EM (single particle) / Resolution: 4.2 Å

36573

8jqi

EMDB-36573, PDB-8jqi:
Cryo EM map of full length PLC gamma 2 and FGFR1 Kinase Domain
Method: EM (single particle) / Resolution: 4.1 Å

PDB-8t7c:
Crystal structure of human phospholipase C gamma 2
Method: X-RAY DIFFRACTION / Resolution: 2.55 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsHYDROLASE / PLCg2 / PLC gamma 2 / Phospholipase C gamma 2 / autoinhibition / signaling / lipid metabolism

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