What specific type of ubiquitin modification targets a protein for degradation?
Polyubiquitin chains linked through Lysine 48 (Lys48) of ubiquitin. This chain is the signal that directs the tagged protein to the proteasome.
What is ubiquitin and what is its primary role?
Ubiquitin is a small protein that is covalently attached to other proteins as a marker in a variety of ways. The major form of ubiquitin addition produces polyubiquitin chains which directs the target protein to the interior of a proteasome.
The Ubiquitin-Proteasome Pathway
The major pathway of selective protein degradation in eukaryotic cells uses ubiquitin as a marker that targets cytosolic and nuclear proteins for rapid proteolysis.
What are the three enzymes involved in ubiquitination?
E1 (Ubiquitin-Activating Enzyme): Activates ubiquitin using ATP.
E2 (Ubiquitin-Conjugating Enzyme): Carries the activated ubiquitin.
E3 (Ubiquitin Ligase): Selects the target protein and catalyzes the transfer of ubiquitin from E2 to the target. It makes sure it doesn’t happen to every protein.
polyubiquitination
a post-translational modification that targets proteins for degradation.
What ubiquitination enzyme is the largest?
E3 so it can recognize proteins.
The Proteasome Structure
It is a large, compartmentalized protease complex with:
Unfoldase Ring: Unfolds the target protein. Recognizes the polyubiquitin tag. It needs ATP to unfold the protein.
Central Cylinder (Core Particle): Contains the sequestered protease active sites that degrade the protein. Its in the tube so it doesn’t cut everything around it.
Endosome
Has no membrane. It changes over time by recieving vesicles from the golgi.
endocytosis
the material to be ingested is progressively enclosed by a small portion of the plasma membrane, which first invaginates and then pinches off to form an endocytic vesicle containing the ingested substance or particle. Eats something from the outside.
Types of endocytosis
Phagocytosis: (“Cell eating”) Uptake of large particles (e.g., bacteria). Receptors will notice that something there.
Pinocytosis: (“Cell drinking”) Constant, non-specific uptake of extracellular fluid and solutes.
Receptor-Mediated Endocytosis: Selective uptake of specific macromolecules. Its a combo of the other two.
What is the function of the early endosome?
most endocytic vesicles fuse with a common receiving compartment, the early endosome, where internalized cargo is sorted: some cargo molecules are returned to the plasma
membrane, either directly or via a recycling endosome, and others remain as the early endosome changes into a late endosome.
What is endosome maturation?
The process by which an early endosome gradually changes into a late endosome. This involves a decrease in pH and the formation of intralumenal vesicles, creating a multivesicular body (MVB). They can then go on to become a lysosome where they degrate things.
What is the role of clathrin in endocytosis?
Most Membrane Invaginations and Pinocytic Vesicles Are Clathrin Coated. It forms a geometrical cage that helps shape the vesicle. Always go outside to inside
Cells Use Receptor-mediated Endocytosis to do what?
Import Selected Extracellular Macromolecules.
● lipids are transported in lipid–protein particles known as low-density lipoproteins (LDLs).
● When a cell needs lipids, it makes transmembrane receptor proteins for LDL at the plasma membrane.
They have receptors on it that cause it to be eaten. There is only a single layer of phosplidids.
Steps of endocytoc pathway
LDL gets coated then uncoated then fusion to early endosome then late endosomes that have vesicules in it. Then it turns into a endolysosome that has hydrolytic enzymes into a lysosome and back into a endolysosome.
Lysosomes
Lysosomes are membrane-enclosed organelles filled with soluble acid hydrolases that digest macromolecules at acidic pH. A vacuolar ATPase in the lysosome membrane uses the energy of ATP hydrolysis to pump H+ into the lysosome, thereby maintaining the lumen at its acidic pH (ph of 5).
What happens if the lysosome breaks
The acidic hydrolases will go out but not do anything because they cant work at ph 7 of the cytoplasm.
How is an endolysosome formed?
Late endosomes containing material received from the plasma membrane by endocytosis and containing newly synthesized lysosomal hydrolases fuse with preexisting lysosomes to form structures that are referred to as endolysosomes, which then fuse with one another. It’s also acidic.
As endosomes mature what happens?
patches of their membrane invaginate to form
intralumenal vesicles. They carry endocytosed membrane proteins
that are to be degraded.
What are Multivesicular Bodies and how are they formed?
MVBs are late endosomes filled with intralumenal vesicles. These vesicles are formed by the inward budding of the endosome membrane, a process mediated by a set of protein complexes called ESCRT (Endosomal Sorting Complexes Required for Transport).
What are the different pathways that deliver cargo to the lysosome?
Endocytosis: Plasma membrane → Endosomes → Lysosome.
Phagocytosis: Large particles → Phagosome → Lysosome.
Autophagy: Cytosolic components/organelles → Autophagosome → Lysosome.
From Golgi: Delivery of newly synthesized lysosomal enzymes.
autophagosome has what
a double membrane
Phagocyotsis
a special form of endocytosis in which a cell uses large
endocytic vesicles called phagosomes to ingest large particles such as
microorganisms and dead cells.
How is phagocytosis initiated?
It is a cargo-triggered process. The binding of a large particle (like a bacterium) to specific cell-surface receptors (e.g., Fc receptors) activates intracellular signaling (e.g., PI 3-kinase) that leads to actin rearrangement and pseudopod extension, engulfing the particle.
