Structural order in Pannexin 1 cytoplasmic domains

Spagnol, Gaëlle; Sorgen, Paul L.; Spray, David C.

doi:10.4161/chan.28854

Cited by 11 publications

(11 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3; Table 1). Notably, a previously identified β-strand 30 aligned with HCS5 (Table 1), though it was not followed by an α-helix, as might be anticipated. The multiple HCS consensus sequences, the general promiscuity of LRR domain secondary structure 13 , and the previously identified mixture of α-helices and β-strands 30 suggest the presence of a putative LRR domain within the Panx1CT.…”

Section: Discussionsupporting

confidence: 52%

“…To start to investigate the possibility of a larger LRR domain within Panx1, we examined the relationship between reported secondary structures commonly associated with LRR motifs/domains and the identified putative LRR and HCS motifs. Since an HCS usually forms a β-sheet and a VS often forms an α-helix 13,17,20 , we examined whether previously reported 30 in silico identified putative secondary structures (partially confirmed using circular dichroism) in the Panx1CT directly aligned with HCS1-HCS5 (Fig. 3; Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the first and last L in the sequence can be replaced by relatively hydrophilic residues. The HCS of the putative LRR motif examined in this study (HC2) is highlighted by a thick border outline.Designated HCS numberMode of discoveryAmino acidsConsensus sequenceOverlapping sites of interestHCS1Visual inspectionL305-L315 L kv Y e I lp T f D Endocytic recognition sequence (Y308-L311) 47 Phosphorylation site (Y308) 48 HCS2ScanPrositeL329-E340 L yn L f L ee N i S or L yn L f L ee N is E Endocytic recognition sequence (Y330-F333) 47 HCS3Visual inspectionY344-S355 Y kc L k V le N i K or Y kc L k V le N ik S Endocytic recognition sequence (Y344-L347) 47 Channel gating, S-Nitrosylation site (C346) 33 ,49 HCS4Visual inspectionI360-M371 I dp M l L lt N l G or I dp M l L lt N lg M Putative membrane-interacting domain (I360-G370) 30 HCS5Visual inspectionI376-T387 I id G k I pt S l Q or I id G k I pt S lq T Caspase-cleavage site (D375-D378) 34,35 β-strand (K373-D380) 30 …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A novel motif in the proximal C-terminus of Pannexin 1 regulates cell surface localization

Epp

Ebert

Sanchez-Arias

et al. 2019

Sci Rep

View full text Add to dashboard Cite

The Pannexin 1 (Panx1) ion and metabolite channel is expressed in a wide variety of cells where it regulates a number of cell behaviours including proliferation and differentiation. Panx1 is expressed on the cell surface as well as intracellular membranes. Previous work suggests that a region within the proximal Panx1 C-terminus (Panx1CT) regulates cell surface localization. Here we report the discovery of a putative leucine-rich repeat (LRR) motif in the proximal Panx1CT necessary for Panx1 cell surface expression in HEK293T cells. Deletion of the putative LRR motif results in significant loss of Panx1 cell surface distribution. Outcomes of complementary cell surface oligomerization and glycosylation state analyses were consistent with reduced cell surface expression of Panx1 LRR deletion mutants. Of note, the oligomerization analysis revealed the presence of putative dimers and trimers of Panx1 at the cell surface. Expression of Panx1 increased HEK293T cell growth and reduced doubling time, while expression of a Panx1 LRR deletion mutant (highly conserved segment) did not reproduce this effect. In summary, here we discovered the presence of a putative LRR motif in the Panx1CT that impacts on Panx1 cell surface localization. Overall these findings provide new insights into the molecular mechanisms underlying C-terminal regulation of Panx1 trafficking and raise potential new lines of investigation with respect to Panx1 oligomerization and glycosylation.

show abstract

Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A novel motif in the proximal C-terminus of Pannexin 1 regulates cell surface localization

Epp

Ebert

Sanchez-Arias

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The region of Panx1 containing the amino acids 191 to 200 has a high propensity to form α helix structure, which are known to constitute a fundamental recognition element in many protein-protein interactions (7, 63). α Helix–mediated protein-protein interactions are practical targets for chemical design of small molecular inhibitors (64).…”

Section: Discussionmentioning

confidence: 99%

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

et al. 2015

View full text Add to dashboard Cite

Both purinergic signaling through nucleotides such as ATP (adenosine 5′-triphosphate) and noradrenergic signaling through molecules such as norepinephrine regulate vascular tone and blood pressure. Pannexin1 (Panx1), which forms large-pore, ATP-releasing channels, is present in vascular smooth muscle cells in peripheral blood vessels and participates in noradrenergic responses. Using pharmacological approaches and mice conditionally lacking Panx1 in smooth muscle cells, we found that Panx1 contributed to vaso-constriction mediated by the α1 adrenoreceptor (α1AR), whereas vasoconstriction in response to serotonin or endothelin-1 was independent of Panx1. Analysis of the Panx1-deficient mice showed that Panx1 contributed to blood pressure regulation especially during the night cycle when sympathetic nervous activity is highest. Using mimetic peptides and site-directed mutagenesis, we identified a specific amino acid sequence in the Panx1 intracellular loop that is essential for activation by α1AR signaling. Collectively, these data describe a specific link between noradrenergic and purinergic signaling in blood pressure homeostasis.

show abstract

“…However, the absence of detectable secondary structure could also be a consequence of instability, in agreement with the relatively low confidence of secondary structure prediction for this region. For example, cytoplasmic domains of connexins have α-helical structure as part of the complete membrane-anchored molecule, or when membrane-tethered, but isolated cytoplasmic domains exhibit detectable helical structure only in aqueous solution containing TFE 35 36 37 . Similarly, the helix-stabilizing effect of TFE in hen lysozyme is observed only in those regions of the polypeptide chain that intrinsically tend to form helical secondary structure elements 38 .…”

Section: Resultsmentioning

confidence: 99%

The cytosolic tail of the tumor marker protein Trop2 - a structural switch triggered by phosphorylation

Pavšič

Ilc

Vidmar

et al. 2015

Sci Rep

View full text Add to dashboard Cite

Trop2 is a transmembrane signaling glycoprotein upregulated in stem and carcinoma cells. Proliferation-enhancing signaling involves regulated intramembrane proteolytic release of a short cytoplasmic fragment, which is later engaged in a cytosolic signaling complex. We propose that Trop2 function is modulated by phosphorylation of a specific serine residue within this cytosolic region (Ser303), and by proximity effects exerted on the cytosolic tail by Trop2 dimerization. Structural characterization of both the transmembrane (Trop2TM) and cytosolic regions (Trop2IC) support this hypothesis, and shows that the central region of Trop2IC forms an α-helix. Comparison of NMR structures of non-phosphorylated and phosphorylated forms suggest that phosphorylation of Trop2IC triggers salt bridge reshuffling, resulting in significant conformational changes including ordering of the C-terminal tail. In addition, we demonstrate that the cytosolic regions of two Trop2 subunits can be brought into close proximity via transmembrane part dimerization. Finally, we show that Ser303-phosphorylation significantly affects the structure and accessibility of functionally important regions of the cytosolic tail. These observed structural features of Trop2 at the membrane-cytosol interface could be important for regulation of Trop2 signaling activity.

show abstract

Structural order in Pannexin 1 cytoplasmic domains

Cited by 11 publications

References 46 publications

A novel motif in the proximal C-terminus of Pannexin 1 regulates cell surface localization

A novel motif in the proximal C-terminus of Pannexin 1 regulates cell surface localization

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

The cytosolic tail of the tumor marker protein Trop2 - a structural switch triggered by phosphorylation

Contact Info

Product

Resources

About