11 - Lecture 11 Announcements 1 Assignments for the week As...

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Announcements : 1. Assignments for the week: As in LG for 9/21 & 9/23; Do PYMOL #4 Hemoglobin 2. Quizzes that have been regraded are at the front, in a green folder Friday's lecture : That the native protein structure has the lowest free energy is not obvious. It is an experimental fact, proven by denaturation/renaturation experiments. Starting from a randomly folded polypeptide, without any other "factors" or "folding enzymes", the Mb native structure folds as the protein is being synthesized on the ribosome (or, after unfolding in a laboratory experiment). For ribonuclease, disulfide bonds must be broken in order to completely unfold this protein, then the disulfides must be re-formed, but still the protein refolds spontaneously into its native structure. All cells need to speed up this "disulfide interchange" process in order that folding is finished in minutes, instead of hours. The enzyme disulfide isomerase does this. Similarly, proteins with Pro residues need some of their peptide bonds at Pro to be changed from trans (as are all peptide bonds when the protein is synthesized on the ribosome) to cis . Prolyl isomerase does this job, and is found in every cell. And one more category of enzymes prevents or can reverse protein misfolding: molecular chaperones In these cases, researchers demonstrated that there was no requirement to find the native structure for “folding machinery” inside the cell. That proteins can fold in such a short time, typically seconds to minutes, is also not well understood. Proteins have internal motion (i.e. different from the entire protein rotating and moving in solution). For HIV protease, part of the protein moves when it binds its peptide substrate. For hexokinase, glucose binding causes a large change in this protein's structure, forming the binding pocket for the other substrate, ATP. In the case of Mb, much smaller movements of the protein occur, thereby providing paths that allow oxygen to get into the protein interior to bind to the heme, and allowing the oxygen also to leave the Mb. How does a protein fold? (1) Perhaps bits of secondary structure form in solution, sometimes the "right" II structures that appear in the final folded protein, sometimes the "wrong" II structures that are not in the final folded protein. But at some point, within seconds or minutes after synthesis on the ribosome, the II structures all come together because of the hydrophobic effect into a structure that is close to the final fold, called a "molten globule". This so-called molten globule is not fully packed, and has extra space and extra motion. Within seconds or perhaps minutes, the final structural domain forms. Or, especially likely for larger proteins, (2) the very first important event might be the
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This note was uploaded on 01/01/2012 for the course BIOMG 3310 taught by Professor Feigenson during the Fall '11 term at Cornell.

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11 - Lecture 11 Announcements 1 Assignments for the week As...

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