Protein Mod in ER Guide 2011

Protein Mod in ER Guide 2011 - Jennifer Stanford, Ph.D....

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Jennifer Stanford, Ph.D. Protein Modifications in the ER Disulfide bond formation: Left: Borrowed from Tom Rapoport. Right: Adapted from Figure 1, Bardwell, J.C.A. (2002) Disulfide Bond Formation, a Race between FAD and Oxygen. Developmental Cell 3:758-60. Disulfide bonds are covalent linkages between two sulfhydryl groups in two adjacent cysteine side chains. Formation of disulfide bonds is essential for the proper folding of many proteins. These bonds help to reinforce the conformation of the protein, thereby stabilizing its structure. The reducing environment of the cytosol does not allow formation of disulfide bonds, and thus they only form in the ER. Disulfide bonds form when the free sulfhydryl groups on cysteines are oxidized. This reaction is catalyzed by protein disulfide isomerase (PDI), using cyteine residues in its active site to help catalyze the reaction. PDI becomes reduced in the process, and must be re-oxidized to allow its participation in another round of oxidation. This reaction depends on the protein endoplasmic reticulum oxidase 1 (Ero1), which contains flavin adenine dinucleotide (FAD) as a prosthetic group. Ero1 also contains a disulfide bond, which is used to regenerate oxidized PDI. Ero1 itself is oxidized by molecular oxygen. Electrons are thought to be passed from thiols in Ero1 to FAD, and then to oxygen. In addition to forming disulfide bonds, PDI can also catalyze rearrangement of disulfide bonds, allowing the enzyme to correct any inappropriate disulfide bonds that are formed as a protein folds. In this case, reduced PDI forms a disulfide bond with the protein, disrupting the disulfide bond in the protein. The protein then continues to fold with PDI attached, and when another disulfide bond can be formed between cysteines within the folding protein, the disulfide bond with PDI will be broken in
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Protein Mod in ER Guide 2011 - Jennifer Stanford, Ph.D....

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