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Protein Trafficking
:''This article deals with protein targeting in eukaryotes unless specified otherwise.'' 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. History In 1970, Günter Blobel conducted experiments on protein translocation across membranes. Blobel, then an assistant professor at Rockefeller University, built upon the work of his colleague George Palade. Palade had previously demonstrated that non-secreted proteins were translated by free ribosomes in the cytosol, while secreted proteins (and target proteins, in general) wer ...
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Eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacteria and Archaea (both prokaryotes) make up the other two domains. The eukaryotes are usually now regarded as having emerged in the Archaea or as a sister of the Asgard archaea. This implies that there are only two domains of life, Bacteria and Archaea, with eukaryotes incorporated among archaea. Eukaryotes represent a small minority of the number of organisms, but, due to their generally much larger size, their collective global biomass is estimated to be about equal to that of prokaryotes. Eukaryotes emerged approximately 2.3–1.8 billion years ago, during the Proterozoic eon, likely as flagellated phagotrophs. Their name comes from the Greek εὖ (''eu'', "well" or "good") and κάρυον (''karyon'', "nut" or "kernel"). Euka ...
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Carboxypeptidase E
Carboxypeptidase E (CPE), also known as carboxypeptidase H (CPH) and enkephalin convertase, is an enzyme that in humans is encoded by the ''CPE'' gene. This enzyme catalyzes the release of C-terminal arginine or lysine residues from polypeptides. CPE is involved in the biosynthesis of most neuropeptides and peptide hormones. The production of neuropeptides and peptide hormones typically requires two sets of enzymes that cleave the peptide precursors, which are small proteins. First, proprotein convertases cut the precursor at specific sites to generate intermediates containing C-terminal basic residues (lysine and/or arginine). These intermediates are then cleaved by CPE to remove the basic residues. For some peptides, additional processing steps, such as C-terminal amidation, are subsequently required to generate the bioactive peptide, although for many peptides the action of the proprotein convertases and CPE is sufficient to produce the bioactive peptide. Tissue distribution ...
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General Overview Of Protein Targeting
A general officer is an officer of high rank in the armies, and in some nations' air forces, space forces, and marines or naval infantry. In some usages the term "general officer" refers to a rank above colonel."general, adj. and n.". OED Online. March 2021. Oxford University Press. https://www.oed.com/view/Entry/77489?rskey=dCKrg4&result=1 (accessed May 11, 2021) The term ''general'' is used in two ways: as the generic title for all grades of general officer and as a specific rank. It originates in the 16th century, as a shortening of ''captain general'', which rank was taken from Middle French ''capitaine général''. The adjective ''general'' had been affixed to officer designations since the late medieval period to indicate relative superiority or an extended jurisdiction. Today, the title of ''general'' is known in some countries as a four-star rank. However, different countries use different systems of stars or other insignia for senior ranks. It has a NATO rank sca ...
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Cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which also comprises the mitochondria, plastids, and other organelles (but not their internal fluids and structures); the cell nucleus is separate. The cytosol is thus a liquid matrix around the organelles. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles. The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and prope ...
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Ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) 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 (rRNA) molecules and many ribosomal proteins (RPs or r-proteins). The ribosomes and associated molecules are also known as the ''translational apparatus''. Overview The sequence of DNA that encodes the sequence of the amino acids in a protein is transcribed into a messenger RNA chain. Ribosomes bind to messenger RNAs and use their sequences for determining the correct sequence of amino acids to generate a given protein. Amino acids are selected and carried to the ribosome by transfer RNA (tRNA) molecules, which enter the ribosome and bind to the messenger RNA chain via an anti-c ...
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MRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is created during the process of Transcription (biology), transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA). This pre-mRNA usually still contains introns, regions that will not go on to code for the final amino acid sequence. These are removed in the process of RNA splicing, leaving only exons, regions that will encode the protein. This exon sequence constitutes mature mRNA. Mature mRNA is then read by the ribosome, and, utilising amino acids carried by transfer RNA (tRNA), the ribosome creates the protein. This process is known as Translation (biology), translation. All of these processes form part of the central dogma of molecular biology, which describes the flow of genet ...
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Translation (biology)
In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or endoplasmic reticulum synthesize proteins after the process of transcription (biology), transcription of DNA to RNA in the cell's nucleus (cell), nucleus. The entire process is called gene expression. In translation, mRNA, messenger RNA (mRNA) is decoded in a ribosome, outside the nucleus, to produce a specific amino acid chain, or polypeptide. The polypeptide later protein folding, folds into an Activation energy, active protein and performs its functions in the Cell (biology), cell. The ribosome facilitates decoding by inducing the binding of Base pair, complementary tRNA anticodon sequences to mRNA codons. The tRNAs carry specific amino acids that are chained together into a polypeptide as the mRNA passes through and is "read" by the ribosome. Translation proceeds in three phases: # Initiation: The ribosome assembles around the target mRNA. The first tRNA is attached a ...
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Posttranslational Modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the mature protein product. PTMs are important components in cell signal transduction, signaling, as for example when prohormones are converted to hormones. Post-translational modifications can occur on the amino acid side chains or at the protein's C-terminus, C- or N-terminus, N- termini. They can extend the chemical repertoire of the 20 standard amino acids by modifying an existing functional group or introducing a new one such as phosphorylation, phosphate. Phosphorylation is a highly effective mechanism for regulating the activity of enzymes and is the most common post-translational modification. Many eukaryotic and prokaryotic proteins also have carbohydra ...
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Protein Folding
Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproducible process, a polypeptide folds into its characteristic three-dimensional structure from a random coil. Each protein exists first as an unfolded polypeptide or random coil after being translated from a sequence of mRNA to a linear chain of amino acids. At this stage the polypeptide lacks any stable (long-lasting) three-dimensional structure (the left hand side of the first figure). As the polypeptide chain is being synthesized by a ribosome, the linear chain begins to fold into its three-dimensional structure. Folding of many proteins begins even during translation of the polypeptide chain. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein (the right hand side of the figure), ...
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Primary Sequence
Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length scales ranging from the level of individual atoms to the relationships among entire protein subunits. This useful distinction among scales is often expressed as a decomposition of molecular structure into four levels: primary, secondary, tertiary, and quaternary. The scaffold for this multiscale organization of the molecule arises at the secondary level, where the fundamental structural elements are the molecule's various hydrogen bonds. This leads to several recognizable ''domains'' of protein structure and nucleic acid structure, including such secondary-structure features as alpha helixes and beta sheets for proteins, and hairpin loops, bulges, and internal loops for nucleic acids. The terms ''primary'', ''secondary'', ''tertiary'', and '' ...
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Signal Patches
A protein signal patch contains information to send a given protein to the indicated location in the cell. It is made up of amino acid residues that are distant to one another in the primary sequence, but come close to each other in the tertiary structure of the folded protein (see red patch in the diagram). Signal patches, unlike some signal sequences, are not cleaved from the mature protein after sorting. They are very difficult to predict. Nuclear localization signals are often signal patches although signal sequences also exist. They are found on proteins destined for the nucleus and enable their selective transport from the cytosol into the nucleus through the nuclear pore complexes. See also * protein targeting * signal peptide A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...
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Peroxisome
A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen peroxide (H2O2) is then formed. Peroxisomes owe their name to hydrogen peroxide generating and scavenging activities. They perform key roles in lipid metabolism and the conversion of reactive oxygen species. Peroxisomes are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, bile acid intermediates (in the liver), D-amino acids, and polyamines, the reduction of reactive oxygen species – specifically hydrogen peroxide – and the biosynthesis of plasmalogens, i.e., ether phospholipids critical for the normal function of mammalian brains and lungs. They also contain approximately 10% of the total activity of two enzymes (Glucose-6-phosphate dehydrogenase and 6-Phosphogluconate dehydrogenase) in the pentose ...
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