University:
Swansea University
Course:
PM-133 | Evolutionary and Molecular Genetics
Academic year:

2023
Views:

269

Pages:

3
Author:

Amal J.

Cotranlational Translocation: Signal Sequence Recognition: SRP (Signal Recognition Particle) binds to the signal sequence on the nascent polypeptide as it emerges from the ribosome. SRP Binding: SRP binds to its receptor on the ER membrane. Translocation Initiation: GTP binds, causing the translocon to open and the ribosome to dock. Protein Translocation: The polypeptide is translocated into the ER lumen as translation continues. Signal Peptidase: The signal sequence is cleaved by signal peptidase. Protein Folding: The translocated polypeptide folds into its proper conformation, often assisted by chaperones. Key Components: SRP: A ribonucleoprotein complex composed of RNA and protein subunits. The P54 subunit binds to the signal sequence. Translocon Channel: Composed of the Sec61 complex in mammals, with subunits Sec61α, Sec61β, and Sec61γ forming the channel. Chaperones: Assist in proper folding of translocated proteins. N-glycosylation Process: Lumenal Side: The synthesis of a glycan precursor begins with N-acetylglucosamine (GlcNAc), followed by the addition of mannose and glucose residues. This process is catalyzed by various glycosyltransferases. Flipping of Glycan: Dolichol phosphate, the lipid carrier, flips the growing glycan from the cytosol to the ER lumen. Mannose and Glucose Addition: Additional mannose and glucose residues are added to the growing glycan chain. The glycan is eventually transferred to a nascent polypeptide. Modification and Trimming: The glycan is further modified in the Golgi apparatus. Transfer to Protein: The glycan is attached to asparagine residues on the protein, completing the N-glycosylation process. Key Inhibitors: Tunamycin: Blocks the addition of GlcNAc to dolichol phosphate, preventing glycosylation. Protein Disulfide Isomerase (PDI): Catalyzes the formation and rearrangement of disulfide bonds in the ER lumen. Disulfide Bond Formation: PDI catalyzes the oxidation of cysteine residues, forming disulfide bonds. Disulfide Bond Rearrangement: PDI assists in the rearrangement of incorrect disulfide bonds to ensure proper protein folding. Key Experiment: Levinthal Paradox: The folding of ribonuclease enzyme was studied, demonstrating that PDI facilitates proper folding by rearranging disulfide bonds. Denaturants like β-mercaptoethanol and urea can disrupt disulfide bonds and hydrophobic interactions, respectively.