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We are analyzing https://www.nature.com/articles/s41467-018-03370-1.

Title:
Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting | Nature Communications
Description:
Sorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes to early endosomes by recognizing phosphatidylinositol 3-phosphate (PI3P) to initiate retromer-mediated segregation of cargoes to the trans-Golgi network (TGN). Here we report the solution structure of full length human SNX3, and show that PI3P recognition is accompanied by bilayer insertion of a proximal loop in its extended Phox homology (PX) domain. Phosphoinositide (PIP) binding is completely blocked by cancer-linked phosphorylation of a conserved serine beside the stereospecific PI3P pocket. This “PIP-stop” releases endosomal SNX3 to the cytosol, and reveals how protein kinases control membrane assemblies. It constitutes a widespread regulatory element found across the PX superfamily and throughout evolution including of fungi and plants. This illuminates the mechanism of a biological switch whereby structured PIP sites are phosphorylated to liberate protein machines from organelle surfaces. Sorting nexin 3 (SNX3) is a phosphatidylinositol 3-phosphate binding protein that localizes to early endosomes. Here the authors use NMR to resolve SNX3′s membrane interactions, revealing that membrane binding is regulated through phosphorylation of a conserved serine by its lipid recognition site.
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Keywords {🔍}

snx, pubmed, article, pip, membrane, google, scholar, cas, fig, protein, structure, binding, sorting, cells, residues, micelles, cell, nature, structures, retromer, proteins, central, phosphorylation, domain, nmr, complex, supplementary, conserved, cpip, nexin, full, bilayer, micelle, biol, data, pocket, receptor, ser, docking, egf, nexins, endosomal, interaction, table, lipid, cancer, site, insertion, endosome, size,

Topics {✒️}

nature portfolio polish-swiss research program privacy policy systems biology research cancer research uk advertising lc-esi-ms/msmass spectrometry 1 mm isopropyl β-d-1-thiogalactopyranoside 13c-edited hsqc-noesy spectra n-terminally his6-tagged protein thermo scientific 13c-edited noesy-hsqc experiments px-bar membrane-remodeling unit nature 449 nature 534 nature reprints snx-bar-mediated endosome tubulation snx3 1h-15n-crosspeak intensities middle development 15n-edited noesy-hsqc 2h/15n/13c labeled protein protease/phosphatase inhibitor cocktail physiological solutions n-terminal histidine tag c-terminal extension exhibiting rabbit-anti eea1 antibody c-terminal extensions pack social media stock solutions vasopressin-sensitive renal cells polyproline type ii helix data-driven micelle docking regulates retromer-motor interaction substantially broadened nmr lines create pip-stops remain anti-parallel β-strands quikchange site-directed mutagenesis facilitate dynein-cargo dissociation defective pi3p-binding site5 extended c-terminal element packed c-terminal hydrophobic mouse anti-egfr antibody β-sheet remains accessible initiate retromer-mediated segregation resonance underwent line broadening wild-type punctate pattern liberate protein machines hrp-labeled secondary antibodies

Schema {🗺️}

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         description:Sorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes to early endosomes by recognizing phosphatidylinositol 3-phosphate (PI3P) to initiate retromer-mediated segregation of cargoes to the trans-Golgi network (TGN). Here we report the solution structure of full length human SNX3, and show that PI3P recognition is accompanied by bilayer insertion of a proximal loop in its extended Phox homology (PX) domain. Phosphoinositide (PIP) binding is completely blocked by cancer-linked phosphorylation of a conserved serine beside the stereospecific PI3P pocket. This “PIP-stop” releases endosomal SNX3 to the cytosol, and reveals how protein kinases control membrane assemblies. It constitutes a widespread regulatory element found across the PX superfamily and throughout evolution including of fungi and plants. This illuminates the mechanism of a biological switch whereby structured PIP sites are phosphorylated to liberate protein machines from organelle surfaces. Sorting nexin 3 (SNX3) is a phosphatidylinositol 3-phosphate binding protein that localizes to early endosomes. Here the authors use NMR to resolve SNX3′s membrane interactions, revealing that membrane binding is regulated through phosphorylation of a conserved serine by its lipid recognition site.
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      headline:Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting
      description:Sorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes to early endosomes by recognizing phosphatidylinositol 3-phosphate (PI3P) to initiate retromer-mediated segregation of cargoes to the trans-Golgi network (TGN). Here we report the solution structure of full length human SNX3, and show that PI3P recognition is accompanied by bilayer insertion of a proximal loop in its extended Phox homology (PX) domain. Phosphoinositide (PIP) binding is completely blocked by cancer-linked phosphorylation of a conserved serine beside the stereospecific PI3P pocket. This “PIP-stop” releases endosomal SNX3 to the cytosol, and reveals how protein kinases control membrane assemblies. It constitutes a widespread regulatory element found across the PX superfamily and throughout evolution including of fungi and plants. This illuminates the mechanism of a biological switch whereby structured PIP sites are phosphorylated to liberate protein machines from organelle surfaces. Sorting nexin 3 (SNX3) is a phosphatidylinositol 3-phosphate binding protein that localizes to early endosomes. Here the authors use NMR to resolve SNX3′s membrane interactions, revealing that membrane binding is regulated through phosphorylation of a conserved serine by its lipid recognition site.
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      name:Biochemistry Department, University of Geneva, Geneva 4, Switzerland
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      name:School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK
      name:Biochemistry Department, University of Geneva, Geneva 4, Switzerland
      name:Biochemistry Department, University of Geneva, Geneva 4, Switzerland
      name:Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada

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