scholarly journals Folding and Insertion of Transmembrane Helices at the ER

2021 ◽  
Vol 22 (23) ◽  
pp. 12778
Author(s):  
Paul Whitley ◽  
Brayan Grau ◽  
James C. Gumbart ◽  
Luis Martínez-Gil ◽  
Ismael Mingarro
Keyword(s):  
Amino Acids ◽  
Endoplasmic Reticulum ◽  
Entry Point ◽  
Eukaryotic Cells ◽  
Helical Conformation ◽  
Aqueous Environment ◽  
Transmembrane Helices ◽  
Endomembrane System ◽  
Membrane Bilayer ◽  
Er Membrane

In eukaryotic cells, the endoplasmic reticulum (ER) is the entry point for newly synthesized proteins that are subsequently distributed to organelles of the endomembrane system. Some of these proteins are completely translocated into the lumen of the ER while others integrate stretches of amino acids into the greasy 30 Å wide interior of the ER membrane bilayer. It is generally accepted that to exist in this non-aqueous environment the majority of membrane integrated amino acids are primarily non-polar/hydrophobic and adopt an α-helical conformation. These stretches are typically around 20 amino acids long and are known as transmembrane (TM) helices. In this review, we will consider how transmembrane helices achieve membrane integration. We will address questions such as: Where do the stretches of amino acids fold into a helical conformation? What is/are the route/routes that these stretches take from synthesis at the ribosome to integration through the ER translocon? How do these stretches ‘know’ to integrate and in which orientation? How do marginally hydrophobic stretches of amino acids integrate and survive as transmembrane helices?

scholarly journals Stitching proteins into membranes, not sew simple

2014 ◽  
Vol 395 (12) ◽  
pp. 1417-1424 ◽  
Author(s):  
Paul Whitley ◽  
Ismael Mingarro
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Protein Assembly ◽  
Integral Membrane Proteins ◽  
Eukaryotic Cells ◽  
Endomembrane System ◽  
Correct Orientation ◽  
Tm Domain ◽  
Er Membrane

Abstract Most integral membrane proteins located within the endomembrane system of eukaryotic cells are first assembled co-translationally into the endoplasmic reticulum (ER) before being sorted and trafficked to other organelles. The assembly of membrane proteins is mediated by the ER translocon, which allows passage of lumenal domains through and lateral integration of transmembrane (TM) domains into the ER membrane. It may be convenient to imagine multi-TM domain containing membrane proteins being assembled by inserting their first TM domain in the correct orientation, with subsequent TM domains inserting with alternating orientations. However a simple threading model of assembly, with sequential insertion of one TM domain into the membrane after another, does not universally stand up to scrutiny. In this article we review some of the literature illustrating the complexities of membrane protein assembly. We also present our own thoughts on aspects that we feel are poorly understood. In short we hope to convince the readers that threading of membrane proteins into membranes is ‘not sew simple’ and a topic that requires further investigation.

scholarly journals The odd one out: Arabidopsis reticulon20 has a role in lipid biosynthesis

2017 ◽  
Author(s):  
Verena Kriechbaumer ◽  
Lilly Maneta-Peyret ◽  
Stanley W Botchway ◽  
Jessica Upson ◽  
Louise Hughes ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Sterol Composition ◽  
Lipid Biosynthesis ◽  
Transmembrane Domains ◽  
Eukaryotic Cells ◽  
The Family ◽  
Er Exit Sites ◽  
Punctate Pattern ◽  
Er Membrane

AbstractThe family of reticulon proteins has been shown to be involved in a variety of functions in eukaryotic cells including tubulation of the endoplasmic reticulum (ER), formation of cell plates and primary plasmodesmata. Reticulons are integral ER membrane proteins characterised by a reticulon homology domain comprising four transmembrane domains which results in the reticulons sitting in the membrane in a W-topology. Here we report on a subgroup of reticulons with an extended N-terminal domain and in particular on arabidopsis reticulon 20. We show that reticulon 20 is located in a unique punctate pattern on the ER membrane. Its closest homologue reticulon 19 labels the whole ER. We show that mutants in RTN20 or RTN19, respectively, display a significant change in sterol composition in the roots indicating a role in lipid biosynthesis or regulation. A third homologue in this family - 3BETAHSD/D1- is localised to ER exit sites resulting in an intriguing location difference for the three proteins.

Identification of topological determinants in the N-terminal domain of transcription factor Nrf1 that control its orientation in the endoplasmic reticulum membrane

2010 ◽  
Vol 430 (3) ◽  
pp. 497-510 ◽  
Author(s):  
Yiguo Zhang ◽  
John D. Hayes
Keyword(s):  
Amino Acids ◽  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Signal Peptide ◽  
Leucine Zipper ◽  
Endoplasmic Reticulum Membrane ◽  
Related Factor ◽  
Terminal Domain ◽  
C Terminus ◽  
Er Membrane

Nrf1 [NF-E2 (nuclear factor-erythroid 2)-related factor 1] is a CNC (cap'n'collar) bZIP (basic-region leucine zipper) transcription factor that is tethered to ER (endoplasmic reticulum) and nuclear envelope membranes through its N-terminal signal peptide (residues 1–30). Besides the signal peptide, amino acids 31–90 of Nrf1 also negatively regulate the CNC-bZIP factor. In the present study we have tested the hypothesis that amino acids 31–90 of Nrf1, and the overlapping NHB2 (N-terminal homology box 2; residues 82–106), inhibit Nrf1 because they control its topology within membranes. This region contains three amphipathic α-helical regions comprising amino acids 31–50 [called the SAS (signal peptide-associated sequence)], 55–82 [called the CRACs (cholesterol-recognition amino acid consensus sequences)] and 89–106 (part of NHB2). We present experimental data showing that the signal peptide of Nrf1 contains a TM1 (transmembrane 1) region (residues 7–24) that is orientated across the ER membrane in an Ncyt/Clum fashion with its N-terminus facing the cytoplasm and its C-terminus positioned in the lumen of the ER. Once Nrf1 is anchored to the ER membrane through TM1, the remaining portion of the N-terminal domain (NTD, residues 1–124) is transiently translocated into the ER lumen. Thereafter, Nrf1 adopts a topology in which the SAS is inserted into the membrane, the CRACs are probably repartitioned to the cytoplasmic side of the ER membrane, and NHB2 may serve as an anchor switch, either lying on the luminal surface of the ER or traversing the membrane with an Ncyt/Clum orientation. Thus Nrf1 can adopt several topologies within membranes that are determined by its NTD.

scholarly journals All aboard!: The secretory pathway

2003 ◽  
Vol 25 (3) ◽  
pp. 10-12
Author(s):  
Stephen High ◽  
Samuel G. Crawshaw
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Membrane Protein ◽  
Cell Surface ◽  
Secretory Pathway ◽  
Entry Point ◽  
Eukaryotic Cells ◽  
Secretory Cells ◽  
Intracellular Membrane ◽  
Biosynthetic Activity

The endoplasmic reticulum (ER) is a major subcellular feature of most eukaryotic cells, and in specialized secretory cells, like those of the pancreas, it densely packs most of the cell. It is the de facto entry point into the secretory pathway and one of its key functions is to provide an extensive intracellular membrane network that supports protein synthesis (Figure 1). This biosynthetic activity is highlighted by the large number of ribosomes that are bound tightly to much of its surface, and it is these ribosomes that synthesize the secretory and membrane protein cargoes that are ultimately destined for export from the ER to the cell surface via the Golgi complex1,2.

scholarly journals Golgi-associated BICD adaptors couple ER membrane penetration and disassembly of a viral cargo

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Chelsey C. Spriggs ◽  
Somayesadat Badieyan ◽  
Kristen J. Verhey ◽  
Michael A. Cianfrocco ◽  
Billy Tsai
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Penetration ◽  
Endomembrane System ◽  
Cellular Membranes ◽  
Nuclear Entry ◽  
Dynein Motor ◽  
Cellular Motor ◽  
Induced Structure ◽  
Er Membrane ◽  
Capsid Disassembly

During entry, viruses must navigate through the host endomembrane system, penetrate cellular membranes, and undergo capsid disassembly to reach an intracellular destination that supports infection. How these events are coordinated is unclear. Here, we reveal an unexpected function of a cellular motor adaptor that coordinates virus membrane penetration and disassembly. Polyomavirus SV40 traffics to the endoplasmic reticulum (ER) and penetrates a virus-induced structure in the ER membrane called “focus” to reach the cytosol, where it disassembles before nuclear entry to promote infection. We now demonstrate that the ER focus is constructed proximal to the Golgi-associated BICD2 and BICDR1 dynein motor adaptors; this juxtaposition enables the adaptors to directly bind to and disassemble SV40 upon arrival to the cytosol. Our findings demonstrate that positioning of the virus membrane penetration site couples two decisive infection events, cytosol arrival and disassembly, and suggest cargo remodeling as a novel function of dynein adaptors.

Prevalence of the pit and antipit in the genus Glycine

1987 ◽  
Vol 45 ◽  
pp. 986-987
Author(s):  
R. W. Yaklich ◽  
E. L. Vigil ◽  
W. P. Wergin
Keyword(s):  
Amino Acids ◽  
Endoplasmic Reticulum ◽  
Glycine Max ◽  
Seed Coat ◽  
Cell Types ◽  
Abaxial Surface ◽  
Legume Seed ◽  
Initial Report ◽  
Cone Cells ◽  
Glycine Max L

The legume seed coat is the site of sucrose unloading and the metabolism of imported ureides and synthesis of amino acids for the developing embryo. The cell types directly responsible for these functions in the seed coat are not known. We recently described a convex layer of tissue on the inside surface of the soybean (Glycine max L. Merr.) seed coat that was termed “antipit” because it was in direct opposition to the concave pit on the abaxial surface of the cotyledon. Cone cells of the antipit contained numerous hypertrophied Golgi apparatus and laminated rough endoplasmic reticulum common to actively secreting cells. The initial report by Dzikowski (1936) described the morphology of the pit and antipit in G. max and found these structures in only 68 of the 169 seed accessions examined.

TMCC3 localizes at the three-way junctions for the proper tubular network of the endoplasmic reticulum

2019 ◽  
Vol 476 (21) ◽  
pp. 3241-3260
Author(s):  
Sindhu Wisesa ◽  
Yasunori Yamamoto ◽  
Toshiaki Sakisaka
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Mammalian Cells ◽  
Coiled Coil ◽  
Transmembrane Domains ◽  
Domain Family ◽  
Coiled Coil Domain ◽  
U2os Cells ◽  
Er Membrane

The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. In this study, we report TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network in U2OS cells. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. These results indicate that TMCC3 localizes at the three-way junctions for the proper tubular ER network.

Spatial localization of unknown proteins in the endoplasmic reticulum predicts functions

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Michael D. Jain ◽  
Hisao Nagaya ◽  
Annalyn Gilchrist ◽  
Miroslaw Cygler ◽  
John J.M. Bergeron
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Protein Synthesis ◽  
Protein Function ◽  
Protein Translocation ◽  
Spatial Localization ◽  
Predict Protein Function ◽  
Insight Into ◽  
Soluble Fractions ◽  
Er Membrane

Protein synthesis, folding and degradation functions are spatially segregated in the endoplasmic reticulum (ER) with respect to the membrane and the ribosome (rough and smooth ER). Interrogation of a proteomics resource characterizing rough and smooth ER membranes subfractionated into cytosolic, membrane, and soluble fractions gives a spatial map of known proteins involved in ER function. The spatial localization of 224 identified unknown proteins in the ER is predicted to give insight into their function. Here we provide evidence that the proteomics resource accurately predicts the function of new proteins involved in protein synthesis (nudilin), protein translocation across the ER membrane (nicalin), co-translational protein folding (stexin), and distal protein folding in the lumen of the ER (erlin-1, TMX2). Proteomics provides the spatial localization of proteins and can be used to accurately predict protein function.

Intramembrane proteolysis and post-targeting functions of signal peptides

2003 ◽  
Vol 31 (6) ◽  
pp. 1243-1247 ◽  
Author(s):  
B. Martoglio
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Bilayer ◽  
Signal Peptide ◽  
Eukaryotic Cells ◽  
Endoplasmic Reticulum Membrane ◽  
Signal Peptides ◽  
Peptide Fragments ◽  
Intramembrane Proteolysis ◽  
Signal Sequences ◽  
Membrane Spanning

Signal sequences are the addresses of proteins destined for secretion. In eukaryotic cells, they mediate targeting to the endoplasmic reticulum membrane and insertion into the translocon. Thereafter, signal sequences are cleaved from the pre-protein and liberated into the endoplasmic reticulum membrane. We have recently reported that some liberated signal peptides are further processed by the intramembrane-cleaving aspartic protease signal peptide peptidase. Cleavage in the membrane-spanning portion of the signal peptide promotes the release of signal peptide fragments from the lipid bilayer. Typical processes that include intramembrane proteolysis is the regulatory or signalling function of cleavage products. Likewise, signal peptide fragments liberated upon intramembrane cleavage may promote such post-targeting functions in the cell.

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