D103 - Lecture 14 - Post-Translational Modifications.docx

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University of California - Irvine
Biological Sciences
Grant Mac Gregor

A. Clicker a. Consequence of phosphor-mimetic mutation (dominant positive) in lamin A i. Nuclear envelope does not assemble properly ii. Intermediate filaments need to be phosphorylated to disassemble iii. Shriveled Nucleus 1. Similar to hutchinson-gilford progeria B. Sec 23/24 a. Interacts with cargo B. Clathrin a. Cannot interact with cargo, even transmembrane proteins b. Requires a adaptor protein to recruit cargo i. AP2 1. At the plasma membrane ii. AP1 1. At the TGN B. FH Patients (Familial hypercholesterolemia) a. Mutation in the sorting signal in the LDL receptor b. LDL receptor cannot bind to the clathrin to be endocytosed c. LDL can still bind to the LDL receptor (stays at the membrane surface) B. Lysosome a. Acidic, pumps protons into the lysosome b. pH dependent enzymes i. Inactive when being transported to the lysosomes b. Lyosome i. Digests material inside the endosome b. Endosome i. Vesicles bud into the endosome ii. Gets rid of membrane receptors by budding into the endosome iii. Lyosome binds iv. Mono-ubiquitination B. Autophagy degrades cytosolic proteins and organelles a. Flattened double membrane encircles the mitochondria b. Autophagic vesicle fuses with the lysosome B. Proteasome a. Core: 50 proteins b. Cap: 16-18 proteins, 6 are ATPase i. Energy for protein unfolding b. Cuts up the proteins c. Degrades poluubiquitinated proteins B. Ubiquitination a. E1 - ubiquitin activating enzyme i. ATP dependent ii. 2 genes b. E2 - Ubiquitin conjugating enzyme i. 35 genes b. E3 - Ubiquitin Ligase i. Creates isopeptide bonds between lysines, and terinal glycine of ubiquitin b. Heavily regulated c. DUBs i. Removes ubiquitin 1. Reversible PTM a. Post translational modification B. Ubiquitin a. Has 7 lysines b. Can be attached at any of its 7 lysines i. Forming linear or branched chains B. Monoubiquitination a. Sorting signal for budding in
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