2.8: Protein localization (2023)

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    In eukaryotic cells, where reactions and proteins are often housed in special membrane-bound compartments (organelles), a system for the directed movement of specific proteins from their site of origin in the cell to their site of origin in the cell must be in place. are used. Cell. In this section we will discuss two main modes of protein localization. We start with the components of theEndomembransystem. This system involves co-translational translocation across membranes and subsequent delivery and processing across various organelles via vesicles and motor protein-mediated transport. It is used for proteins that function in the compartments of the endomembrane system, for proteins that are embedded in the plasma membrane, and for secreted proteins.

    We will also discuss another mode of protein targeting and translocation. This broad class of protein-gated mechanisms is strictly post-translational, directing proteins to the nucleus, mitochondria, plastids, and peroxisomes. Certain concepts, such as signal peptides, are common to the endomembrane system targeting mentioned above.

    Discussion: So far in this lesson you have seen many types of proteins. Name some of these proteins and their location in the cell. For example, where would you expect to find glycolytic enzymes?

    design challenge

    Eukaryotic cells contain membrane-bound organelles that effectively separate materials, processes, and reactions from each other and from the cytoplasm. This in itself poses a problem: how can the cell control the placement of materials between these organelles? More specifically, how does a eukaryotic cell transport compounds from their place of origin (in most cases, the cytoplasm) to where they are needed (perhaps the nucleus, mitochondria, or cell surface)?

    Does the above design challenge sound familiar? This challenge was presented in the Eukaryotes section of the course. We discussed the need for network highways that would allow directed movement of vesicles from one location to another.

    Protein translocation and the endomembrane system

    In eukaryotes, all mRNAs are bound by cytoplasmic ribosomes and translation begins in the cytoplasm. However, some proteins lack the first amino acids (the N-terminal most) to provide proteinsfunction(They'll be cut out later anyway, as we'll see) but rather to provide the proteinsAddress. If the protein to be translated needs to be transported somewhere else (basically somewhere other than the cytoplasm), it willsignal sequence, a continuous stretch of amino acids recognized by aSignal Recognition Particle (SRP). Different SRPs recognize different signal sequences.

    When a protein is destined to become part of the endomembrane system (ER, Golgi, endosomes, plasma membrane, or secreted by the cell), the emergence of the signal peptide and its uptake by its associated SRP results in the ribosome being switched off. Translation cannot proceed until the SRP is removed. The resulting complex diffuses through the cell until it contacts an SRP receptor on the surface of the rough ER. The ribosome bound to the SRP "docks" to the rough surface of the ER at a transmembrane channeltranslokon. When the ribosome binds to the translocon, the SRP is released and the ribosome can continue to translate the protein. The translocon opens wide enough for the newly made protein to go directly into the lumen, or membrane, of the rough ER.

    2.8: Protein localization (1)

    ER translocon complex. Polymerization takes place in the ribosomes (yellow and light blue). The newly synthesized protein is transported through the membrane (grey) into the interior of the ER via the ER translocon (green: Sec61, blue: TRAP complex and red: oligosaccharyltransferase complex). Sec61 is the protein conduction channel and the OST adds sugar groups to the nascent protein.

    Discussion: When the SRP binds to the growing peptide chain and the ribosome, the ribosome stops. What do you think that means? What do you think would happen if the ribosome could keep translating the mRNA while the SRP was bound?


    From this point on, the protein has entered the bodyEndomembransystem. The rough ER membrane is the manufacturing site of all transmembrane proteins, as well as the proteins for the Golgi apparatus, lysosomes, endosomes, cell membranes, and more. Because there are many options for protein targets, the coarse ER is involved in the co-translational sorting of the proteins that contain specific signal sequences. Proteins destined for similar locations are packaged into transport vesicles that emerge from the rough ER membrane. These vesicles fuse together to form the cis flake of the Golgi (closest to the nucleus). The lumen of Golgi contains enzymes that recognize specific sequences on their target proteins and modify their targets. Many types of post-translational modifications take place as the protein matures in the Golgi. The phosphorylation of oligosaccharides on lysosomal proteins occurs in thecisside of the Golgi apparatus, while galactose, sialic acid and other carbohydrates can be added to the proteins contained thereintransside of the Golgi apparatus. These post-translational modifications can change the structure and function of the protein and also serve as a signal that helps determine the final destination of the protein. By the time the proteins reappear (in vesicles again), different proteins with the same address have been sorted into the same vesicles (you might want to visualize this process).here).

    2.8: Protein localization (2)

    The endomembrane system

    Vesicle movement (also described in the Eukaryotes module) is an energy-intensive process involving microtubules and motor proteins. Vesicles are too large to effectively diffuse into the cell. Motor proteins transport vesicles and their cargo by traveling in one direction along microtubules. As the motor proteins move along the microtubules, chemical energy is converted to mechanical energy in the form of ATP.

    How do vesicles “know” that they have reached their destination?

    Microtubule-based transport results in vesicles being repeatedly pushed or pulled in a general direction (ie, away from the nucleus). In cells that are much longer than they are wide (neurons, root hairs), vesicle transport can be quite dramatic.However, kinesins do not "know" that they go to the plasma membrane, for example, and not to the lysosomal membrane. They only help spread their load. In fact, it's the vesicle itself that recognizes its target (although it couldn't move without the motor protein). SNARE proteins embedded in the vesicle and its target recognize each other and facilitate the fusion of the vesicle with the membrane of its target compartment. For example, these proteins facilitate the release of neurotransmitters that allow neurons to transmit intercellular signals. The same SNAREs are attacked by many neurotoxins, including botulinum toxin (Botox). The inhibition of neurotransmitter release by Botox leads to a flaccid paralysis of the muscles.

    Energy history:Write an energy history for vesicular transport in the cell. Include a description of the overall process and the initial and final states of energy used in the process. What is generally done?

    Other protein transport systems

    There are many organelles to which their proteins are not deliveredabovethe endomembrane system, such as the nucleus, mitochondria, and chloroplasts.Encode proteins sorted into non-endomembrane compartmentsdes Signalpeptids, but their translocation is not related to translation. These proteins are fully translated in the cytoplasm, although they are often immediately bound by chaperonins that prevent their folding.

    Protein translocation into the nucleus

    Discussion: Hypothesize how scientists might go about discovering a nuclear localization signal. What experiments/data do you need to determine if a sequence is a nuclear localization signal?

    Nuclear pore complexes are called closed channels and act as selective gates that can transport specific macromolecules in and out of the nucleus. Smaller proteins (<30 kDal) do not need to be recognized by this complex, but are free to pass through it. However, larger proteins must bear a specific peptide motif called anuclear localization signals(NLS).

    Nuclear localization signals are detected byImported, small proteins that recognize and bind to the nuclear localization signal. A protein bound to importins can interact with the nuclear pore complex and enter the nucleus through the canal. The importin acts as a "passport" to the core.

    Discussion: Several different nuclear localization signals have been found in nuclear proteins. These signals contain multiple lysine and arginine residues. What are the chemical properties of lysine and arginine? What does that tell you about the possible chemical properties of importins?

    Protein translocation in mitochondria

    About 10% of the proteins in a eukaryotic cell are located in the mitochondria. The mitochondrion itself only synthesizes about 11-12 proteins and therefore has to import most of its proteins from the cytoplasm. Mitochondrial proteins are fully synthesized before crossing the mitochondrial membrane. These proteins have an N-terminal targeting signal that folds into a strongly basic (+ charged) amphipathic alpha helix. Once this signal sequence exits the ribosome, a cytoplasmic chaperone protein recognizes and binds to the signal, ultimately connecting the protein/ribosome complex to the mitochondrial outer membrane.

    On the surface of the mitochondria, the signaling sequence is inserted from the N-terminus into a protein-conduction channel (called a tom) that moves the protein across the outer membrane and, depending on the signaling sequences present, into the protein-conduction channel of the inner membrane. (called Tim). Note that there are many possible targets for a mitochondrial protein (just like for plastid proteins). Signaling sequences in the protein itself interact with recognition proteins in the mitochondrion to determine the protein's final location.

    The ultimate destination of a mitochondrial protein (outer membrane, intermembrane space, inner membrane, or matrix) is determined by its specific set of signaling sequences.

    2.8: Protein localization (3)


    What does it mean for a protein to be localized? ›

    In order for subcellular processes to be carried out within defined compartments or cellular regions, mechanisms must exist to ensure the required protein components are present at the sites and at an adequate concentration. The accumulation of a protein at a given site is known as protein localization.

    Where is the localization of protein? ›

    Cells are organized into many different compartments such as the cytosol, nucleus, endoplasmic reticulum (ER), and mitochondria. Almost all proteins are made in the cytosol, yet each cellular compartment requires a specific set of proteins.

    What is protein localization in the plasma membrane? ›

    protein localization to plasma membrane Gene Ontology Term (GO:0072659) Definition: A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane.

    How do proteins localize to the ER? ›

    Protein localization to the ER often depends on certain sequences of amino acids located at the N terminus or C terminus. These sequences are known as signal peptides, molecular signatures, or sorting signals.

    Why is localization of a protein important? ›

    Genome organization and subnuclear protein localization are essential for normal cellular function and have been implicated in the control of gene expression, DNA replication, and genomic stability.

    What does localized mean in pathology? ›

    A localized disease is an infectious or neoplastic process that originates in and is confined to one organ system or general area in the body, such as a sprained ankle, a boil on the hand, an abscess of finger.

    What do you mean by Localisation? ›

    Localization is the adaptation of a product or service to meet the needs of a particular language, culture or desired population's "look-and-feel." A successfully localized service or product is one that appears to have been developed within the local culture.

    What organelle is responsible for protein localization? ›

    The cell organelle that is responsible for the process of protein synthesis is the ribosome. A ribosome is a non-membranous organelle that is also known as the "protein factory of the cell". It is composed of two sub-units that vary in their sizes.

    What is protein localization to organelle? ›

    establishment of protein localization to organelle

    The directed movement of a protein to a specific location on or in an organelle. Encompasses establishment of localization in the membrane or lumen of a membrane-bounded organelle.

    What is meant by membrane localisation? ›

    DEFINITION. Any process by which a substance or cellular entity, such as a protein complex or organelle, is transported to, and/or maintained in, a specific location within or in the membrane of a cell.

    What is protein localization to the nucleus? ›

    protein localization to nucleus Gene Ontology Term (GO:0034504) Definition: A process in which a protein transports or maintains the localization of another protein to the nucleus.

    How do cells localize proteins? ›

    As we have seen, proteins often localize by binding to another protein or proteins that are already sequestered at a particular location in the cell.

    What method can be used to localize proteins in cells? ›

    Proteins can be imaged in cells by tagging them with fluorescent proteins or antibodies.

    How is a protein inserted into the ER membrane? ›

    Abstract. Membrane proteins are inserted into the endoplasmic reticulum (ER) by two highly conserved parallel pathways. The well-studied co-translational pathway uses signal recognition particle (SRP) and its receptor for targeting and the SEC61 translocon for membrane integration.

    What does localized mean in biology? ›

    Definition: Any process in which a cell, a substance, or a cellular entity, such as a protein complex or organelle, is transported, tethered to or otherwise maintained in a specific location. In the case of substances, localization may also be achieved via selective degradation.

    What does localized mean in microbiology? ›

    Localisation. 1. The determination of the site or place of any process or lesion. 2. Restriction to a circumscribed or limited area.

    What does localized content mean? ›

    What is Content Localization? In the context of digital marketing, content localization is the process of creating (or translating) specialized content for a specific region or international country.

    What does it mean to get localized? ›

    : to assign to or keep within a definite locality. intransitive verb. : to accumulate in or be restricted to a specific or limited area. an infection that localizes in the ear.


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