Determinants of Endoplasmic Reticulum-to-Lipid Droplet Protein Targeting.

Amino Acid Motifs / genetics Animals Cell Membrane / genetics Drosophila Proteins / genetics Drosophila melanogaster / genetics Endoplasmic Reticulum / genetics Energy Metabolism / genetics Glycerol-3-Phosphate O-Acyltransferase / genetics Hydrophobic and Hydrophilic Interactions Lipid Droplets / metabolism N-Acetylglucosaminyltransferases / genetics Tryptophan / metabolism
LiveDrop UDP-N-acetylglucosaminyltransferase subunit endoplasmic reticulum glycerol-3-phosphate acyltransferase 4 lipid droplets protein targeting

Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
24 08 2020
Historique:
received: 11 11 2019
revised: 11 05 2020
accepted: 07 07 2020
pubmed: 31 7 2020
medline: 29 1 2021
entrez: 31 7 2020
Statut: ppublish

Résumé

Lipid droplet (LD) formation from the endoplasmic reticulum (ER) is accompanied by the targeting and accumulation of specific hydrophobic, membrane-embedded proteins on LDs. The determinants of this process are unknown. Here, we study the hydrophobic membrane motifs of two Drosophila melanogaster proteins, GPAT4 and ALG14, that utilize this pathway, and we identify crucial sequence features that mediate LD accumulation. Molecular dynamics simulations and studies in cells reveal that LD targeting of these motifs requires deeply inserted tryptophans that have lower free energy in the LD oil phase and positively charged residues near predicted hairpin hinges that become less constrained in the LD environment. Analyzing hydrophobic motifs from similar LD-targeting proteins, it appears that the distribution of tryptophan and positively charged residues distinguishes them from non-LD-targeting membrane motifs. Our studies identify specific sequence features and principles of hydrophobic membrane motifs that mediate their accumulation on LDs.

Identifiants

DOI: 10.1016/j.devcel.2020.07.001 PMID: 32730754 PMC: PMC7696655
pubmed: 32730754
pii: S1534-5807(20)30549-9
doi: 10.1016/j.devcel.2020.07.001
pmc: PMC7696655
mid: NIHMS1617288
pii:
doi:

Substances chimiques

Drosophila Proteins 0
Tryptophan 8DUH1N11BX
Glycerol-3-Phosphate O-Acyltransferase EC 2.3.1.15
gpat4 protein, Drosophila EC 2.3.1.51
N-Acetylglucosaminyltransferases EC 2.4.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

471-487.e7

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM097194
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124348
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Maria-Jesus Olarte (MJ)

Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06510, USA.

Siyoung Kim (S)

Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.

Morris E Sharp (ME)

Department of Chemistry, James Franck Institute, and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.

Jessica M J Swanson (JMJ)

Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: j.swanson@utah.edu.

Robert V Farese (RV)

Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02124, USA. Electronic address: robert@hsph.harvard.edu.

Tobias C Walther (TC)

Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02124, USA. Electronic address: twalther@hsph.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structure secondaire des protéines › Motifs d'acides aminés › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Eucaryotes › Animaux › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines d'arthropode › Protéines d'insecte › Protéines de Drosophila › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Arthropodes › Insectes › Pterygota › Neoptera › Holometabola › Diptera › Drosophilidae › Drosophila › Drosophila melanogaster › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Réticulum endoplasmique › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Métabolisme › Métabolisme énergétique › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Acyltransferases › Glycerol 3-phosphate acyltransferase › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Phénomènes chimiques › Interactions hydrophobes et hydrophiles › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Gouttelettes lipidiques › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Glycosyltransferase › N-acetylhexosaminyltransferase › N-acetylglucosaminyltransferase › Determinants of Endoplasmic Reticulum-to-Lipid...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés essentiels › Tryptophane › Determinants of Endoplasmic Reticulum-to-Lipid...