Syntactic Approach to Predict Membrane Spanning Regions of Transmembrane Proteins

2005 ◽  
pp. 95-104
Author(s):  
Koliya Pulasinghe ◽  
Jagath C. Rajapakse
Keyword(s):  
Transmembrane Proteins ◽  
Syntactic Approach ◽  
Membrane Spanning

scholarly journals Cotranslational Intersection between the SRP and GET Targeting Pathways to the Endoplasmic Reticulum of Saccharomyces cerevisiae

2016 ◽  
Vol 36 (18) ◽  
pp. 2374-2383 ◽  
Author(s):  
Ying Zhang ◽  
Thea Schäffer ◽  
Tina Wölfle ◽  
Edith Fitzke ◽  
Gerhard Thiel ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Transmembrane Domain ◽  
Signal Recognition Particle ◽  
Transmembrane Proteins ◽  
Signal Recognition ◽  
Ribosome Binding ◽  
Channel Proteins ◽  
Membrane Spanning ◽  
Combined Data

Targeting of transmembrane proteins to the endoplasmic reticulum (ER) proceeds via either the signal recognition particle (SRP) or the guided entry of tail-anchored proteins (GET) pathway, consisting of Get1 to -5 and Sgt2. While SRP cotranslationally targets membrane proteins containing one or multiple transmembrane domains, the GET pathway posttranslationally targets proteins containing a single C-terminal transmembrane domain termed the tail anchor. Here, we dissect the roles of the SRP and GET pathways in the sorting of homologous, two-membrane-spanning K+channel proteins termed Kcv, Kesv, and Kesv-VV. We show that Kcv is targeted to the ER cotranslationally via its N-terminal transmembrane domain, while Kesv-VV is targeted posttranslationally via its C-terminal transmembrane domain, which recruits Get4-5/Sgt2 and Get3. Unexpectedly, nascent Kcv recruited not only SRP but also the Get4-5 module of the GET pathway to ribosomes. Ribosome binding of Get4-5 was independent of Sgt2 and was strongly outcompeted by SRP. The combined data indicate a previously unrecognized cotranslational interplay between the SRP and GET pathways.

scholarly journals Dunking into the Lipid Bilayer: How Direct Membrane Binding of Nucleoporins Can Contribute to Nuclear Pore Complex Structure and Assembly

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3601
Author(s):  
Mohamed Hamed ◽  
Wolfram Antonin
Keyword(s):  
Nuclear Envelope ◽  
Current Knowledge ◽  
Complex Structure ◽  
Transmembrane Proteins ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Membrane Spanning ◽  
Pore Complexes ◽  
And Function ◽  
Membrane Spanning Domains

Nuclear pore complexes (NPCs) mediate the selective and highly efficient transport between the cytoplasm and the nucleus. They are embedded in the two membrane structure of the nuclear envelope at sites where these two membranes are fused to pores. A few transmembrane proteins are an integral part of NPCs and thought to anchor these complexes in the nuclear envelope. In addition, a number of nucleoporins without membrane spanning domains interact with the pore membrane. Here we review our current knowledge of how these proteins interact with the membrane and how this interaction can contribute to NPC assembly, stability and function as well as shaping of the pore membrane.

Regulated intramembrane proteolysis: from the endoplasmic reticulum to the nucleus

2002 ◽  
Vol 38 ◽  
pp. 155-168 ◽  
Author(s):  
Robert B Rawson
Keyword(s):  
Endoplasmic Reticulum ◽  
Regulatory Element ◽  
Transmembrane Proteins ◽  
Intramembrane Proteolysis ◽  
Regulated Intramembrane Proteolysis ◽  
Class 1 ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Membrane Spanning ◽  
Highly Hydrophobic

Regulated intramembrane proteolysis (Rip) is an ancient and widespread process by which cells transmit information from one compartment (the endoplasmic reticulum) to another (the nucleus). Two separate cleavages that are carried out by two separate proteases are required for Rip. The first protease cleaves its protein substrate within an extracytoplasmic domain; the second cleaves it within a membrane-spanning domain, releasing a functionally active fragment of the target protein. In eukaryotes, examples of Rip can be divided into two classes, according to the proteases that are involved and the orientation of the substrates with the membrane. Class 1 Rip involves type 1 transmembrane proteins and requires presenilin for cleavage within a membrane-spanning domain. In Class 2 Rip, the highly hydrophobic metalloprotease, site-2 protease, is required for cleavage within a membrane-spanning domain and substrates are type 2 transmembrane proteins. Both classes of Rip are implicated in diseases that are important in modern societies, such as hyperlipidaemias (via the sterol regulatory element binding protein pathway) and Alzheimer's disease (via processing of the amyloid precursor protein.)

rstand its paraloguekirreact redundantly during embryonic muscle development inDrosophila

Development ◽  
2001 ◽  
Vol 128 (21) ◽  
pp. 4229-4239 ◽  
Author(s):  
Martin Strünkelnberg ◽  
Bernhard Bonengel ◽  
Livia M. Moda ◽  
Alexander Hertenstein ◽  
H. Gert de Couet ◽  
...  
Keyword(s):  
Muscle Development ◽  
Expression Patterns ◽  
Transmembrane Proteins ◽  
Complete Failure ◽  
Embryonic Muscle ◽  
Founder Cells ◽  
Membrane Spanning ◽  
Fusion Competent Myoblasts ◽  
Embryonic Muscle Development ◽  
Null Mutants

The polynucleate myotubes of vertebrates and invertebrates form by fusion of myoblasts. We report the involvement of the Drosophila melanogaster Roughest (Rst) protein as a new membrane-spanning component in this process. Rst is strongly expressed in mesodermal tissues during embryogenesis, but rst null mutants display only subtle embryonic phenotypes. Evidence is presented that this is due to functional redundancy between Rst and its paralogue Kirre. Both are highly related single-pass transmembrane proteins with five extracellular immunoglobulin domains and three conserved motifs in the intracellular domain. The expression patterns of kirre and rst overlap during embryonic development in muscle founder cells. Simultaneous deletion of both genes causes an almost complete failure of fusion between muscle founder cells and fusion-competent myoblasts. This defect can be rescued by one copy of either gene. Moreover, Rst, like Kirre is a myoblast attractant.

The topogenic fate of the polytopic transmembrane proteins, synaptophysin and connexin, is determined by their membrane-spanning domains

1995 ◽  
Vol 108 (3) ◽  
pp. 883-894 ◽  
Author(s):  
R.E. Leube
Keyword(s):  
Endoplasmic Reticulum ◽  
Gap Junctions ◽  
De Novo ◽  
Point Mutations ◽  
Transmembrane Proteins ◽  
Transmembrane Domains ◽  
Parent Molecule ◽  
Transmembrane Segments ◽  
Genes Expression ◽  
Membrane Spanning

The synaptophysins and connexins are polytopic transmembrane proteins of similar secondary structure that accumulate as multiple homo-oligomers in specialized membrane regions, the presynaptic transmitter vesicles or gap junctions. Transfection and expression of the respective genes in cultured epithelial cells results in the de novo formation of either small cytoplasmic, synaptophysin-rich vesicles, or functional gap junctions consisting of clustered connexin molecules. To examine the molecular requirements for the specific enrichment and topogenesis of both types of molecule, chimeric cDNAs were constructed composed of different parts of the rat synaptophysin and rat liver connexin32 genes. Expression of the encoded chimeric polypeptides in hepatocellular carcinoma-derived cells showed that only chimeras with all four transmembrane domains from either parent molecule were delivered to their specific destination. In contrast, chimeras with transmembrane domains from both connexin32 and synaptophysin were always retained in the endoplasmic reticulum. The topogenic nature of the transmembrane domains was further demonstrated by deletion mutagenesis, indicating that removal of cytoplasmic end domains or intravesicular loops does not abolish targeting. On the other hand, excision of individual transmembrane domains or introduction of point mutations in transmembrane segments resulted in retention in the endoplasmic reticulum.

scholarly journals Evidence that the COOH terminus of human presenilin 1 is located in extracytoplasmic space

2005 ◽  
Vol 289 (3) ◽  
pp. C576-C581 ◽  
Author(s):  
Young S. Oh ◽  
R. James Turner
Keyword(s):  
Amino Acids ◽  
Membrane Protein ◽  
Early Onset ◽  
Transmembrane Proteins ◽  
Presenilin 1 ◽  
Type I ◽  
Terminal Amino ◽  
Β Amyloid ◽  
Membrane Spanning ◽  
Polytopic Membrane Protein

The polytopic membrane protein presenilin 1 (PS1) is a component of the γ-secretase complex that is responsible for the intramembranous cleavage of several type I transmembrane proteins, including the β-amyloid precursor protein (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have been genetically linked to early-onset familial Alzheimer’s disease. PS1 contains 10 hydrophobic regions (HRs) sufficiently long to be α-helical membrane spanning segments. Most topology models for PS1 place its COOH terminal ∼40 amino acids, which include HR 10, in the cytosolic space. However, several recent observations suggest that HR 10 may be integrated into the membrane and involved in the interaction between PS1 and APP. We have applied three independent methodologies to investigate the location of HR 10 and the extreme COOH terminus of PS1. The results from these methods indicate that HR 10 spans the membrane and that the COOH terminal amino acids of PS1 lie in the extracytoplasmic space.

Polycystin expression is temporally and spatially regulated during renal development

1997 ◽  
Vol 272 (5) ◽  
pp. F602-F609 ◽  
Author(s):  
J. Van Adelsberg ◽  
S. Chamberlain ◽  
V. D'Agati
Keyword(s):  
Plasma Membranes ◽  
Predicted Amino Acid Sequence ◽  
Renal Development ◽  
Polycystic Kidney ◽  
Fetal Kidney ◽  
Spatial Regulation ◽  
Adult Kidney ◽  
A Cell ◽  
Autosomal Dominant Polycystic Kidney ◽  
Membrane Spanning

Mutations in PKD1 cause autosomal dominant polycystic kidney disease (ADPKD), a common genetic disease in which cysts form from kidney tubules. The predicted product of this gene is a novel protein with cell-adhesive and membrane-spanning domains. To test the hypothesis that polycystin, the product of the PKD1 gene, is a cell adhesion molecule, we raised antibodies against peptides derived from the unduplicated, membrane-spanning portion of the predicted amino acid sequence. These antibodies recognized membrane-associated polypeptides of 485 and 245 kDa in human fetal kidney homogenates. Expression was greater in fetal than adult kidney by both Western blot analysis and immunofluorescence. In fetal kidney, polycystin was localized to the plasma membranes of ureteric bud and comma and S-shaped bodies. However, in more mature tubules in fetal kidney, in adult kidney, and in polycystic kidney, the majority of polycystin staining was intracellular. The temporal and spatial regulation of polycystin expression during renal development lead us to speculate that polycystin may play a role in nephrogenesis.

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