14.3 Post-translational modifications and protein targeting
3 min read•august 7, 2024
Proteins undergo crucial modifications after synthesis, shaping their function and destination. , , , and fine-tune protein behavior, while signal sequences guide them to specific cellular locations.
Proper folding is key for protein function. assist in this process, preventing aggregation and misfolding. The ER and play vital roles in modifying, sorting, and packaging proteins for their final destinations.
Post-translational Modifications
Glycosylation and Phosphorylation
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- Glycosylation involves the addition of carbohydrate groups to proteins
- Occurs in the and Golgi apparatus
- Glycosylation can affect , solubility, and function
- Phosphorylation is the addition of phosphate groups to proteins by kinases
- Phosphorylation can activate or deactivate proteins, modulating their function
- Plays a crucial role in pathways (insulin signaling)
Ubiquitination and Acetylation
- Ubiquitination is the attachment of ubiquitin molecules to proteins
- Marks proteins for degradation by the proteasome
- Regulates and helps maintain
- Acetylation involves the addition of acetyl groups to proteins, typically on lysine residues
- Can affect protein stability, localization, and interactions with other molecules
- Histone acetylation plays a role in regulating gene expression (chromatin remodeling)
Protein Targeting and Sorting
Signal Sequence and Endoplasmic Reticulum
- Signal sequences are short peptide sequences that direct proteins to specific cellular compartments
- Typically located at the N-terminus of a protein
- Signal sequences are recognized by the (SRP)
- SRP directs the ribosome-nascent polypeptide complex to the endoplasmic reticulum (ER)
- In the ER, the is cleaved, and the protein undergoes further modifications (glycosylation)
Golgi Apparatus and Secretory Pathway
- The Golgi apparatus is a series of flattened membrane sacs that modify, sort, and package proteins
- Proteins are transported from the ER to the Golgi via
- Within the Golgi, proteins undergo further modifications (glycosylation, sulfation)
- Proteins are sorted and packaged into secretory vesicles for transport to their final destination
- The involves the transport of proteins from the ER through the Golgi to the plasma membrane or extracellular space
- (hormones, enzymes) are released from the cell via exocytosis
Protein Folding and Quality Control
Protein Folding and Chaperone Proteins
- is the process by which a polypeptide chain acquires its native three-dimensional structure
- Proper folding is essential for protein function and stability
- can aggregate and cause cellular dysfunction (Alzheimer's disease, Parkinson's disease)
- Chaperone proteins assist in the folding process and help prevent protein aggregation
- Examples of chaperone proteins include (Hsp70, Hsp90)
- Chaperones bind to unfolded or partially folded proteins and provide a favorable environment for proper folding
- Chaperones also help refold misfolded proteins and target irreversibly misfolded proteins for degradation
- The endoplasmic reticulum has a quality control system that ensures only properly folded proteins are transported to the Golgi
- Misfolded proteins in the ER are retained and targeted for degradation via the ER-associated degradation (ERAD) pathway
Key Terms to Review (21)
Acetylation: Acetylation is a chemical modification that involves the addition of an acetyl group (COCH₃) to a molecule, typically proteins, which can influence their function and activity. This process plays a crucial role in post-translational modifications, altering the properties of proteins such as their stability, localization, and interactions with other biomolecules. By affecting these properties, acetylation is integral to regulating various cellular processes including gene expression and metabolism.
Cell Signaling: Cell signaling is the process by which cells communicate with each other to coordinate their functions, respond to environmental changes, and maintain homeostasis. This communication occurs through various signaling molecules, receptors, and pathways that transmit information across cell membranes, influencing cellular activities like growth, differentiation, and metabolism. Understanding cell signaling is essential to grasp how biomolecules like proteins and lipids interact within these processes and how post-translational modifications can affect the targeting and function of these signaling proteins.
Cellular homeostasis: Cellular homeostasis refers to the processes and mechanisms that cells use to maintain a stable internal environment, despite external changes. This balance is crucial for cellular functions, including metabolism, growth, and response to stimuli, ensuring that conditions like pH, ion concentration, and temperature remain within optimal ranges. Proper homeostasis allows cells to function efficiently and adapt to varying conditions in their environment.
Chaperone Proteins: Chaperone proteins are specialized molecules that assist in the proper folding and stabilization of other proteins, ensuring they achieve their functional conformations. They play crucial roles in preventing misfolding and aggregation, which can lead to cellular stress and diseases. By facilitating the folding process, chaperones also influence the post-translational modifications and targeting of proteins to their specific cellular locations.
Disulfide Bonds: Disulfide bonds are covalent linkages formed between the sulfur atoms of two cysteine residues in proteins, playing a critical role in stabilizing protein structures. These bonds help maintain the three-dimensional shape of proteins, influencing their stability and function by providing rigidity and resistance to denaturation. The formation and rearrangement of disulfide bonds can also occur during post-translational modifications, which impact how proteins interact within cellular environments.
Endoplasmic reticulum: The endoplasmic reticulum (ER) is a membranous organelle found in eukaryotic cells that plays a crucial role in the synthesis, folding, modification, and transport of proteins and lipids. This network of tubules and flattened sacs is divided into two types: rough ER, which is studded with ribosomes and primarily involved in protein synthesis, and smooth ER, which is associated with lipid synthesis and detoxification processes. The ER is integral for post-translational modifications and protein targeting to ensure proper protein function and localization within the cell.
Glycosylation: Glycosylation is the biochemical process by which carbohydrates, or sugars, are covalently attached to proteins or lipids. This modification can significantly influence the structure and function of the molecules involved, playing a crucial role in various biological processes such as cell signaling, immune response, and protein stability.
Golgi apparatus: The Golgi apparatus is an organelle in eukaryotic cells that functions primarily in the modification, sorting, and packaging of proteins and lipids for secretion or delivery to other organelles. It plays a crucial role in post-translational modifications, where newly synthesized proteins are processed and modified before they reach their final destinations within or outside the cell.
Heat shock proteins: Heat shock proteins (HSPs) are a group of highly conserved proteins that play a critical role in protein folding and protection under stress conditions, such as elevated temperatures. They help refold misfolded proteins and prevent aggregation, ensuring cellular homeostasis during stressful events. HSPs are vital in post-translational modifications and protein targeting as they assist in guiding newly synthesized polypeptides to their functional conformations and cellular locations.
Misfolded proteins: Misfolded proteins are proteins that do not achieve their correct three-dimensional structure, which is essential for their proper function. When proteins misfold, they can aggregate or form abnormal structures that can disrupt cellular processes and lead to diseases. These misfolded proteins often arise due to errors during synthesis or post-translational modifications, impacting their targeting and functionality within the cell.
Phosphorylation: Phosphorylation is a biochemical process involving the addition of a phosphate group ( ext{PO}_4^{3-}) to a molecule, typically a protein or nucleotide. This modification can change the function, activity, or location of the molecule, making it crucial for regulating various biological processes. It plays a significant role in cellular signaling and metabolism, influencing how cells respond to their environment and interact with each other.
Protein activity regulation: Protein activity regulation refers to the mechanisms that control the activity of proteins, ensuring that they function correctly within a biological context. This regulation is crucial for maintaining cellular homeostasis and involves various processes such as post-translational modifications, allosteric regulation, and protein degradation. Through these mechanisms, proteins can be activated or deactivated in response to different stimuli, allowing cells to adapt to changing conditions.
Protein folding: Protein folding is the process by which a linear chain of amino acids acquires its three-dimensional functional structure. This process is crucial because the specific shape of a protein determines its function and interaction with other molecules. Proper folding ensures that proteins can perform their roles effectively within biological systems, impacting everything from enzyme activity to cell signaling.
Protein stability: Protein stability refers to the ability of a protein to maintain its three-dimensional structure and functional integrity under various environmental conditions. This concept is crucial because the functionality of proteins often depends on their proper folding and structural conformation, which can be affected by factors like temperature, pH, and the presence of other molecules. Understanding protein stability helps in studying how proteins are modified after synthesis and how they are directed to specific cellular locations.
Protein turnover: Protein turnover refers to the continuous process of synthesis and degradation of proteins within a cell, allowing for the dynamic regulation of protein levels and functions. This process is essential for maintaining cellular homeostasis, adapting to changes in the environment, and facilitating cellular repair and renewal. It connects closely to post-translational modifications and protein targeting, as these modifications can influence the stability, localization, and functional capacity of proteins during their lifecycle.
Secreted proteins: Secreted proteins are proteins that are synthesized within a cell and then exported outside of that cell to perform various functions. These proteins play crucial roles in cellular communication, immune responses, and the maintenance of physiological processes. Their journey from synthesis to secretion involves specific post-translational modifications and targeting mechanisms that ensure they reach their intended destination.
Secretory pathway: The secretory pathway is the cellular process through which proteins are synthesized, modified, and transported to their final destinations, often outside the cell or to specific organelles. This pathway is essential for maintaining cellular functions and involves various cellular structures, including the endoplasmic reticulum (ER), Golgi apparatus, and vesicles. Understanding this process is crucial as it also involves post-translational modifications that impact protein targeting and function.
Signal recognition particle: The signal recognition particle (SRP) is a ribonucleoprotein complex that plays a critical role in targeting nascent polypeptides to the endoplasmic reticulum (ER) during protein synthesis. It recognizes and binds to the signal peptide of a growing polypeptide chain as it emerges from the ribosome, facilitating the transport of the ribosome-polypeptide complex to the ER membrane for proper localization and processing.
Signal sequence: A signal sequence is a short peptide chain that directs the transport of a newly synthesized protein to its appropriate cellular location. This sequence typically consists of hydrophobic amino acids and serves as a tag that ensures proteins are correctly targeted for secretion, membrane insertion, or localization within organelles. The presence of a signal sequence is crucial for the proper functioning of proteins within the cell.
Transport vesicles: Transport vesicles are small, membrane-bound sacs that transport molecules within cells, particularly proteins and lipids, from one organelle to another or to the cell membrane for secretion. They play a crucial role in the secretory and endocytic pathways, ensuring that proteins undergo necessary modifications and are delivered to their correct destinations within the cell or outside of it.
Ubiquitination: Ubiquitination is a post-translational modification process in which a small protein called ubiquitin is attached to a target protein, marking it for degradation or altering its function. This modification plays a critical role in regulating various cellular processes, including protein turnover, signal transduction, and DNA repair, highlighting its importance in maintaining cellular homeostasis.