7344_lecture_sum - Week 1 Introduction Introduction of...

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Week 1 Introduction. Introduction of instructors, students, and course Overview of translation (ribosome, ribosomal proteins, rRNA, mRNA, tRNA, translation factors, genetic code) We will watch the amazing mini movie “Elongation Cycle of Protein Biosynthesis” by Agrawal, Whiting & Frank starring the E. coli ribosome, tRNA and elongation factors. Protein synthesis is one of the most fundamental cellular processes in a living cell. Protein synthesis occurs on the ribosome. It is composed of three distinct steps: INITIATION, ELONGATION and TERMINATION. Although protein synthesis is highly conserved in all kingdoms of life, there are critical structural and functional differences between prokaryotes and eukaryotes. In this first class, we will review the ordered events in protein synthesis and review the function of the various components of the translation machinery. We will discuss high- resolution structures of the prokaryotic and eukaryotic ribosome obtained by x-ray crystallography and cryo-electron microscopy and how these structures help us understand the mechanism of action of toxins, antibiotics and other protein synthesis inhibitors covered later in the course. Sit back and enjoy a fantastic voyage through the most incredible molecular machine: The Ribosome! Week 2 Toxins I: Toxins that target the ribosome - Ricin and Shiga toxin. In 1978, a very small amount of Ricin was used by the KGB to kill a Bulgarian Soviet political dissident in London, and Ricin is still considered to be one of the most serious bio-terrorist threats. Many organisms produce toxic proteins that exert lethal activity towards other cells. Ricin is an extremely potent protein toxin produced by the castor bean plant and has no known antidote. A single molecule will inactivate almost 2000 ribosomes within a minute. The bacterial Shiga toxin is also extremely potent. Interestingly, both Ricin and Shiga toxin are ribosome-inactivating proteins and target the eukaryotic ribosome large subunit in a similar fashion. We will discuss the experimental techniques and data that explain how Ricin and Shiga toxin specifically target the 60S ribosomal subunit and why they are so potent. Week 3 Toxins II: Toxins that target eukaryotic elongation factor 2 - Diphtheria toxin and Pseudomonas exotoxin A. Diphtheria, a respiratory tract infection, is caused by the gram-positive Corynebacterium diphtheriae ; the mortality rate of diphtheria is 5-10 %. Diphtheria toxin (DT) is one of the most studied and best-understood bacterial toxins. Both Diphtheria toxin and Pseudomonas exotoxin A target eukaryotic elongation factor 2 (eEF-2) by covalent
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modification of diphthamide, a unique modified amino acid in the protein. We will
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This note was uploaded on 11/11/2011 for the course BIO 7.344 taught by Professor Bobsauer during the Spring '08 term at MIT.

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7344_lecture_sum - Week 1 Introduction Introduction of...

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