scholarly journals Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gβ5

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eunyoung Jeong ◽  
Yoojoong Kim ◽  
Jihong Jeong ◽  
Yunje Cho
Keyword(s):  
Growth Factor ◽  
Coiled Coil ◽  
Protein Signaling ◽  
Synaptic Development ◽  
Induced Mood ◽  
Epidermal Growth ◽  
Class C ◽  
Tm Domain ◽  
Intracellular Loops ◽  
Orphan Gpcr

AbstractGPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among class C GPCRs, GPR158 is unique as it lacks a Venus flytrap-fold ligand-binding domain and terminates Gαi/o protein signaling through the RGS7-Gβ5 heterodimer. Here, we report the cryo-EM structures of GPR158 alone and in complex with one or two RGS7-Gβ5 heterodimers. GPR158 dimerizes through Per-Arnt-Sim-fold extracellular and transmembrane (TM) domains connected by an epidermal growth factor-like linker. The TM domain (TMD) reflects both inactive and active states of other class C GPCRs: a compact intracellular TMD, conformations of the two intracellular loops (ICLs) and the TMD interface formed by TM4/5. The ICL2, ICL3, TM3, and first helix of the cytoplasmic coiled-coil provide a platform for the DHEX domain of one RGS7 and the second helix recruits another RGS7. The unique features of the RGS7-binding site underlie the selectivity of GPR158 for RGS7.

Epidermal Growth Factor Tethered through Coiled-Coil Interactions Induces Cell Surface Receptor Phosphorylation

2009 ◽  
Vol 20 (8) ◽  
pp. 1569-1577 ◽  
Author(s):  
Cyril Boucher ◽  
Benoît Liberelle ◽  
Mario Jolicoeur ◽  
Yves Durocher ◽  
Gregory De Crescenzo
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Coiled Coil ◽  
Cell Surface Receptor ◽  
Receptor Phosphorylation ◽  
Surface Receptor ◽  
Epidermal Growth

Human corneal epithelial cell response to epidermal growth factor tethered via coiled-coil interactions

Biomaterials ◽  
2010 ◽  
Vol 31 (27) ◽  
pp. 7021-7031 ◽  
Author(s):  
Cyril Boucher ◽  
Juan-Carlos Ruiz ◽  
Marc Thibault ◽  
Michael D. Buschmann ◽  
Michael R. Wertheimer ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Epidermal Growth Factor ◽  
Cell Response ◽  
Coiled Coil ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial ◽  
Human Corneal Epithelial Cell ◽  
Epidermal Growth

scholarly journals The Coiled-Coil Domain of Stat3 Is Essential for Its SH2 Domain-Mediated Receptor Binding and Subsequent Activation Induced by Epidermal Growth Factor and Interleukin-6

2000 ◽  
Vol 20 (19) ◽  
pp. 7132-7139 ◽  
Author(s):  
Tong Zhang ◽  
Wei Hua Kee ◽  
Kah Tong Seow ◽  
Winnie Fung ◽  
Xinmin Cao
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Receptor Binding ◽  
Interleukin 6 ◽  
Coiled Coil ◽  
Sh2 Domain ◽  
Stat Proteins ◽  
Coiled Coil Domain ◽  
Epidermal Growth

ABSTRACT STAT proteins are a family of latent transcription factors that mediate the response to various cytokines and growth factors. Upon stimulation by cytokines, STAT proteins are recruited to the receptors via their SH2 domains, phosphorylated on a specific tyrosine, dimerized, and translocated into the nucleus, where they bind specific DNA sequences and activate the target gene transcription. STATs share highly conserved structures, including an N-domain, a coiled-coil domain, a DNA-binding domain, a linker domain, and an SH2 domain. To investigate the role of the coiled-coil domain, we performed a systematic deletion analysis of the N-domain and each of the α-helices and mutagenesis of conserved residues in the coiled-coil region of Stat3. Our results indicate that the coiled-coil domain is essential for Stat3 recruitment to the receptor and the subsequent tyrosine phosphorylation and tyrosine phosphorylation-dependent activities, such as dimer formation, nuclear translocation, and DNA binding, stimulated by epidermal growth factor (EGF) or interleukin-6 (IL-6). Single mutation of Asp170 or, to a lesser extent, Lys177 in α-helix 1 diminishes both receptor binding and tyrosine phosphorylation. Furthermore, the Asp170 mutant retains its ability to bind to DNA when phosphorylated on Tyr705 by Src kinase in vitro, implying a functional SH2 domain. Finally, we demonstrate a direct binding of Stat3 to the receptor. Taken together, our data reveal a novel role for the coiled-coil domain that regulates the early events in Stat3 activation and function.

scholarly journals Dimerization is required for SH3PX1 tyrosine phosphorylation in response to epidermal growth factor signalling and interaction with ACK2

2006 ◽  
Vol 394 (3) ◽  
pp. 693-698 ◽  
Author(s):  
Chandra Childress ◽  
Qiong Lin ◽  
Wannian Yang
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Intracellular Localization ◽  
Coiled Coil ◽  
Dimerization Domain ◽  
Bar Domain ◽  
Tyrosine Kinase 2 ◽  
C Terminus ◽  
Epidermal Growth

SH3PX1 [SNX9 (sorting nexin 9)] is a member of SNX super-family that is recognized by sharing a PX (phox homology) domain. We have previously shown that SH3PX1, phosphorylated by ACK2 (activated Cdc42-associated tyrosine kinase 2), regulates the degradation of EGF (epidermal growth factor) receptor. In mapping the tyrosine phosphorylation region, we found that the C-terminus of SH3PX1 is required for its tyrosine phosphorylation. Further analysis indicates that this region, known as the coiled-coil domain or the BAR (Bin–amphiphysin–Rvs homology) domain, is the dimerization domain of SH3PX1. Truncation of as little as 13 amino acid residues at the very C-terminus in the coiled-coil/BAR domain of SH3PX1 resulted in no dimerization, no ACK2-catalysed and EGF-stimulated tyrosine phosphorylation and no interaction with ACK2. The intracellular localization of SH3PX1 became dysfunctional upon truncation in the BAR domain. Taken together, our results indicate that the dimerization, which is mediated by the BAR domain, is essential for the intracellular function of SH3PX1.

scholarly journals GIT1 Functions as a Scaffold for MEK1-Extracellular Signal-Regulated Kinase 1 and 2 Activation by Angiotensin II and Epidermal Growth Factor

2004 ◽  
Vol 24 (2) ◽  
pp. 875-885 ◽  
Author(s):  
Guoyong Yin ◽  
Judith Haendeler ◽  
Chen Yan ◽  
Bradford C. Berk
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Coiled Coil ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Upstream Kinase ◽  
Epidermal Growth

ABSTRACT Activation of the mitogen-activated protein kinase pathway represented by extracellular signal-regulated kinases (ERK1/2) and activation of the upstream kinase (MEK1) are critical events for growth factor signal transduction. c-Src has been proposed as a common mediator for these signals in response to both G protein-coupled receptors (GPCRs) and tyrosine kinase-coupled receptors (TKRs). Here we show that the GPCR kinase-interacting protein 1 (GIT1) is a substrate for c-Src that associates with MEK1 in vascular smooth-muscle cells and human embryonic kidney 293 cells. GIT1 binding via coiled-coil domains and a Spa2 homology domain is required for sustained activation of MEK1-ERK1/2 after stimulation with angiotensin II and epidermal growth factor. We propose that GIT1 serves as a scaffold protein to facilitate c-Src-dependent activation of MEK1-ERK1/2 in response to both GPCRs and TKRs.

scholarly journals MICAL-like1 mediates epidermal growth factor receptor endocytosis

2011 ◽  
Vol 22 (18) ◽  
pp. 3431-3441 ◽  
Author(s):  
Nancy Abou-Zeid ◽  
Rudy Pandjaitan ◽  
Lucie Sengmanivong ◽  
Violaine David ◽  
Gwenaelle Le Pavec ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Fluorescent Protein ◽  
Coiled Coil ◽  
Growth Factor Receptor ◽  
Time Lapse ◽  
Small Gtpase ◽  
Rab Protein ◽  
Epidermal Growth

Small GTPase Rabs are required for membrane protein sorting/delivery to precise membrane domains. Rab13 regulates epithelial tight junction assembly and polarized membrane transport. Here we report that Molecule Interacting with CasL (MICAL)-like1 (MICAL-L1) interacts with GTP-Rab13 and shares a similar domain organization with MICAL. MICAL-L1 has a calponin homology (CH), LIM, proline rich and coiled-coil domains. It is associated with late endosomes. Time-lapse video microscopy shows that green fluorescent protein–Rab7 and mcherry-MICAL-L1 are present within vesicles that move rapidly in the cytoplasm. Depletion of MICAL-L1 by short hairpin RNA does not alter the distribution of a late endosome/lysosome-associated protein but affects the trafficking of epidermal growth factor receptor (EGFR). Overexpression of MICAL-L1 leads to the accumulation of EGFR in the late endosomal compartment. In contrast, knocking down MICAL-L1 results in the distribution of internalized EGFR in vesicles spread throughout the cytoplasm and promotes its degradation. Our data suggest that the N-terminal CH domain associates with the C-terminal Rab13 binding domain (RBD) of MICAL-L1. The binding of Rab13 to RBD disrupts the CH/RBD interaction, and may induce a conformational change in MICAL-L1, promoting its activation. Our results provide novel insights into the MICAL-L1/Rab protein complex that can regulate EGFR trafficking at late endocytic pathways.

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