Membrane bound polyribosome

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In cell biology, membrane bound polyribosomes are attached to a cell's endoplasmic reticulum. [1] When certain proteins are synthesized by a ribosome they can become "membrane-bound". The newly produced polypeptide chains are inserted directly into the endoplasmic reticulum by the ribosome and are then transported to their destinations. Bound ribosomes usually produce proteins that are used within the cell membrane or are expelled from the cell via exocytosis . [2]

Contents

Background

A membrane-bound polyribosome, as the name suggests, is composed of multiple ribosomes that are associated with a membrane. Proteins are synthesized via messenger ribonucleic acid (mRNA) from the nucleus being released either into the cytoplasm or into the rough endoplasmic reticulum. [3] The rough endoplasmic reticulum branches off of the cell nucleus, has multiple cisternae or layered folds that have interstitial space for protein extrusion. [3] Ribosomes are located in both the cytosol, cellular fluid, or rough endoplasmic reticulum and attach to this ribonucleic acid by separation and re-association of subunits around the messenger ribonucleic acid. [3] In eukaryotic cells, the small subunit (40S) stays on one side and translates the messenger ribonucleic acid while the large subunit (60S) goes codon by codon down the mRNA and attaches each amino acids coded for making a polypeptide. [3] [4] A polysome is when multiple ribosomes attach to the same strand of messenger ribonucleic acid. [3] The polypeptides ribosomes produce go on to be cell structural proteins, enzymes, and many other things. [3] Ribosomes can also sometimes be associated with chloroplasts and mitochondria but these are not membrane bound. [3]

The image shows a membrane-bound ribosome synthesizing a protein into the lumen of the endoplasmic reticulum. Image by wiki user Christinelmiller. Rough ER Close up.png
The image shows a membrane-bound ribosome synthesizing a protein into the lumen of the endoplasmic reticulum. Image by wiki user Christinelmiller.

Origin

Free-floating ribosomes can become membrane bound through a process called translocation. [5] Through translocation, ribosomes that are found in the cytosol producing proteins are moved and attached to the membrane. [3] This process is responsible for development of the rough endoplasmic reticulum. [3] First, ribosomes begin protein synthesis at the N-terminus. [3] The first of the polypeptide may actually be a signal sequence that tells the ribosome that the protein must be extruded into the rough endoplasmic reticulum. [3] The signal sequence triggers translocation by binding with a signal recognition particle (SRP) also located in the cytosol. [3] The signal recognition particle allows recognition and binding via a signal recognition particle receptor on the target membrane’s surface. [3] The signal recognition particle receptor and signal recognition particle are both attached to a translocon and bound with guanosine triphosphate (GTP). [3] This guanosine triphosphate is phosphorylated for energy and opens the translocon allowing the ribosome to attach via its 60S subunit and its signal sequence to enter the lumen, or institial space of the rough endoplasmic reticulum. [3] The signal recognition particle and signal recognition particle receptor detach and can be recycled. [3] The signal sequence is cleaved inside the lumen of the rough endoplasmic reticulum and the ribosome continues to produce the protein into the endoplasmic reticulum where it is folded. [3] Upon protein synthesis completion, the translocon closes and the ribosome detaches. It is important to remember that during translocation, translation briefly stops until binding with the membrane is finished. [3] It is also important to remember that ribosomes can associate and dissociate with the endoplasmic reticulum as need for protein synthesis. [6] After synthesis into the rough endoplasmic reticulum, proteins may travel to the end of the rough endoplasmic reticulum where they are exocytosed, or packaged into small vesicles formed via cleavage of the membrane of the rough endoplasmic reticulum. These vesicles are sent to the Golgi apparatus for sorting and release as needed by the cell. [3] Some proteins are made to be released immediately as the cell is in constant need of them while some proteins are store for immediate release upon signal. [3]

The image shows the translocation of a ribosome and the role of the SRP. Image by wiki user Czwieb. SRPFunction2.png
The image shows the translocation of a ribosome and the role of the SRP. Image by wiki user Czwieb.

The idea that translation and translocation occur simultaneously except in some yeasts was confirmed via microsomes. [3] Microsomes are small vesicles of rough endoplasmic reticulum's membranes formed after disruption of the organelle via homogenation. [7] Homogenation is physical disruption of cells. [7] Microsomes form after homogenization because of the membrane nature of the endoplasmic reticulum. [3] In a lipid bilayer, hydrophobic tails must come together and be hydrophilic head must face the external aqueous environment. [3] In an experiment, proteins were synthesized via ribosomes with microsomes added simultaneously and with microsomes added after synthesis. [3] In the group where microsomes were added simultaneously, the proteins were synthesized into the microsome with the signal sequence cleaved. [3] In the group where microsomes were added post protein synthesis, the proteins were located outside the microsome and retained their signal sequence. [3] Therefore, it is possible to tell if a protein has been extruded into a microsome by its length (lack of a N-terminal signal protein if extruded), resistance to proteases, lack of resistance to proteases in the presence of detergents, and glycosylation. [3] It was confirmed that non-extruded proteins are longer via SDS-page of proteins in the presence of and without microsomes. [3] Protease resistance is due to the characteristics of the surrounding endoplasmic reticulum. [3] And glycosylation occurs via glycosyltransferases to help with folding and stabilization of proteins. [3]

Significance

The cleavage of a signal protein, resistance to proteases, and glycosylation provided by the endoplasmic reticulum to membrane-bound polyribosomes allows for more effective protein production. [3] Presence of the signal protein makes the protein bulkier, a different shape, and harder to store until the unusable signal sequence can be cleaved. [3] The protection from proteases due to protection by the endoplasmic reticulum prevents the protein from being degraded as it is formed. [3] Extrusion in the endoplasmic reticulum also makes sure that the protein folds correctly. [3] Resident endoplasmic reticulum proteins like binding protein (BiP), protein disulfide isomerase (PDI), and glycosyltransferases (GTs) are all responsible for ensuring correct protein folding and stabilization as the protein is assembled. [3] Binding protein can actively help fold or prevent folding of proteins while protein disulfide isomerase promotes the formation of disulfide bridges. [3] Glycosyltransferases promotes the glycosylation or incorporation of a carbohydrate to improve rigidity or structure of a protein. [3] Failure of proteins to fold correctly may result in the unfolded protein response. [3] Unfolded proteins cause swelling of the endoplasmic reticulum as more unfolded proteins continue to be produced. [3] The unfolded protein response can result in endoplasmic reticulum stress, phosphorylation of PERK, phosphorylation of elF2a, down regulation of protein production, and possibly apoptosis. [3] Apoptosis of affected cells may result in a disease like Amylotrophic Lateral Sclerosis (ALS). [3] In Amylotrophic Lateral Sclerosis, dendritic cells undergo endoplasmic reticulum stress because of misfiled SOD1 proteins and apoptose resulting in lack of nerve transmission and loss of muscle control. [3] Eventually, those with Amylotrophic Lateral Sclerosis die because of lack of nerve impulses to signal breathing or heart ventricle contraction.

Related Research Articles

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that synthesizes, folds and processes proteins

The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae, and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.

<span class="mw-page-title-main">Endomembrane system</span> Membranes in the cytoplasm of a eukaryotic cell

The endomembrane system is composed of the different membranes (endomembranes) that are suspended in the cytoplasm within a eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles. In eukaryotes the organelles of the endomembrane system include: the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, lysosomes, vesicles, endosomes, and plasma (cell) membrane among others. The system is defined more accurately as the set of membranes that forms a single functional and developmental unit, either being connected directly, or exchanging material through vesicle transport. Importantly, the endomembrane system does not include the membranes of plastids or mitochondria, but might have evolved partially from the actions of the latter.

<span class="mw-page-title-main">Protein biosynthesis</span> Assembly of proteins inside biological cells

Protein biosynthesis is a core biological process, occurring inside cells, balancing the loss of cellular proteins through the production of new proteins. Proteins perform a number of critical functions as enzymes, structural proteins or hormones. Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences.

Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.

<span class="mw-page-title-main">Ribosome</span> Intracellular organelle consisting of RNA and protein functioning to synthesize proteins

Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomal RNA is found in the ribosomal nucleus where this synthesis happens. Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.

The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes.

A signal peptide is a short peptide present at the N-terminus of most newly synthesized proteins that are destined toward the secretory pathway. These proteins include those that reside either inside certain organelles, secreted from the cell, or inserted into most cellular membranes. Although most type I membrane-bound proteins have signal peptides, most type II and multi-spanning membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which biochemically resembles a signal sequence except that it is not cleaved. They are a kind of target peptide.

The translocon is a complex of proteins associated with the translocation of polypeptides across membranes. In eukaryotes the term translocon most commonly refers to the complex that transports nascent polypeptides with a targeting signal sequence into the interior space of the endoplasmic reticulum (ER) from the cytosol. This translocation process requires the protein to cross a hydrophobic lipid bilayer. The same complex is also used to integrate nascent proteins into the membrane itself. In prokaryotes, a similar protein complex transports polypeptides across the (inner) plasma membrane or integrates membrane proteins. In either case, the protein complex are formed from Sec proteins, with the heterotrimeric Sec61 being the channel. In prokaryotes, the homologous channel complex is known as SecYEG.

In cell biology, microsomes are heterogeneous vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.

Sec61, termed SecYEG in prokaryotes, is a membrane protein complex found in all domains of life. As the core component of the translocon, it transports proteins to the endoplasmic reticulum in eukaryotes and out of the cell in prokaryotes. It is a doughnut-shaped pore through the membrane with 3 different subunits (heterotrimeric), SecY (α), SecE (γ), and SecG (β). It has a region called the plug that blocks transport into or out of the ER. This plug is displaced when the hydrophobic region of a nascent polypeptide interacts with another region of Sec61 called the seam, allowing translocation of the polypeptide into the ER lumen.

<span class="mw-page-title-main">Oligosaccharyltransferase</span> Class of enzymes

Oligosaccharyltransferase or OST (EC 2.4.1.119) is a membrane protein complex that transfers a 14-sugar oligosaccharide from dolichol to nascent protein. It is a type of glycosyltransferase. The sugar Glc3Man9GlcNAc2 (where Glc=Glucose, Man=Mannose, and GlcNAc=N-acetylglucosamine) is attached to an asparagine (Asn) residue in the sequence Asn-X-Ser or Asn-X-Thr where X is any amino acid except proline. This sequence is called a glycosylation sequon. The reaction catalyzed by OST is the central step in the N-linked glycosylation pathway.

TRAPP (TRAnsport Protein Particle) is a protein involved in particle transport between organelles.

A secretory protein is any protein, whether it be endocrine or exocrine, which is secreted by a cell. Secretory proteins include many hormones, enzymes, toxins, and antimicrobial peptides. Secretory proteins are synthesized in the endoplasmic reticulum.

<span class="mw-page-title-main">Signal recognition particle receptor</span>

Signal recognition particle (SRP) receptor, also called the docking protein, is a dimer composed of 2 different subunits that are associated exclusively with the rough ER in mammalian cells. Its main function is to identify the SRP units. SRP is a molecule that helps the ribosome-mRNA-polypeptide complexes to settle down on the membrane of the endoplasmic reticulum.

The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. It has been found to be conserved between mammalian species, as well as yeast and worm organisms.

<span class="mw-page-title-main">Ribophorin</span>

Ribophorins are dome shaped transmembrane glycoproteins which are located in the membrane of the rough endoplasmic reticulum, but are absent in the membrane of the smooth endoplasmic reticulum. There are two types of ribophorines: ribophorin I and II. These act in the protein complex oligosaccharyltransferase (OST) as two different subunits of the named complex. Ribophorin I and II are only present in eukaryote cells.

<span class="mw-page-title-main">RRBP1</span> Protein-coding gene in the species Homo sapiens

Ribosome-binding protein 1, also referred to as p180, is a protein that in humans is encoded by the RRBP1 gene.

<span class="mw-page-title-main">Sec61 alpha 1</span>

Protein transport protein Sec61 subunit alpha isoform 1 is a protein that in humans is encoded by the SEC61A1 gene.

<span class="mw-page-title-main">SSR2</span> Protein-coding gene in the species Homo sapiens

Translocon-associated protein subunit beta also known as TRAP-beta is a protein that in humans is encoded by the SSR2 gene.

David Domingo Sabatini is an Argentine-American cell biologist and the Frederick L. Ehrman Professor Emeritus of Cell Biology in the Department of Cell Biology at New York University School of Medicine, which he chaired from 1972 to 2011. Sabatini's major research interests have been on the mechanisms responsible for the structural complexity of the eukaryotic cell. Throughout his career, Sabatini has been recognized for his efforts in promoting science in Latin America.

References

  1. ↑ Seiser, Robert M.; Nicchitta, Christopher V. (2000). "The Fate of Membrane-bound Ribosomes Following the Termination of Protein Synthesis". Journal of Biological Chemistry. 275 (43): 33820–33827. doi: 10.1074/jbc.M004462200 . PMID   10931837 . Retrieved 29 October 2017.
  2. ↑ Bhardwaj, Uma; Bhardwaj, Ravindra. Biochemistry for Nurses. Pearson Education India. p. 11. ISBN   9788131795286.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 Lodish, Harvey (April 1, 2016). Molecular Cell Biology (8th ed.). N/A: W. H. Freeman. pp. Whole book. ISBN   978-1464183393.
  4. ↑ Gregory, Brian; Rahman, Nusrat; Bommakanti, Ananth; Shamsuzzaman, Md; Thapa, Mamata; Lescure, Alana; Zengel, Janice M; Lindahl, Lasse (2019-03-05). "The small and large ribosomal subunits depend on each other for stability and accumulation". Life Science Alliance. 2 (2): e201800150. doi:10.26508/lsa.201800150. ISSN   2575-1077. PMC   6402506 . PMID   30837296.
  5. ↑ Fewell, Sheara W.; Brodsky, Jeffrey L. (2013). Entry into the Endoplasmic Reticulum: Protein Translocation, Folding and Quality Control. Landes Bioscience.
  6. ↑ Sanvictores, Terrence; Davis, Donald D. (2022), "Histology, Rough Endoplasmic Reticulum", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   33085273 , retrieved 2022-12-07
  7. 1 2 de Araújo, Mariana E. G.; Lamberti, Giorgia; Huber, Lukas A. (2015-11-02). "Homogenization of Mammalian Cells". Cold Spring Harbor Protocols. 2015 (11): 1009–1012. doi:10.1101/pdb.prot083436. ISSN   1559-6095. PMID   26527761.
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