Protein degradation.pptx how do proteins degrade

Physiology Lectures for PharmD students (Pakistan)

1. Dr. Salman Ul Islam Unit#1 BASIC CELL FUNCTIONS Topic : Proteins degradation Physiology-A

2. A protein is made of amino acids linked together into a polypeptide chain. The amino acids are linked by peptide bonds to form a polypeptide backbone of repeating structure ( gray boxes), from which the side chain of each amino acid projects. The sequence of these chemically distinct side chains—which can be nonpolar ( green ), polar uncharged ( yellow ), positively charged ( red  ), or negatively charged ( blue )—gives each protein its distinct, individual properties. A small polypeptide of just four amino acids is shown here. Proteins are typically made up of chains of several hundred amino acids, whose sequence is always presented starting with the N-terminus and read from left to right.

3. Three types of noncovalent bonds help proteins fold. Although a single one of any of these bonds is quite weak, many of them together can create a strong bonding arrangement that stabilizes a particular three-dimensional structure, as in the small polypeptide shown in the center. R is often used as a general designation for an amino acid side chain. Protein folding is also aided by hydrophobic forces.

4. Hydrophobic forces help proteins fold into compact conformations. In a folded protein, polar amino acid side chains tend to be displayed on the surface, where they can interact with water; nonpolar amino acid side chains are buried on the inside to form a tightly packed hydrophobic core of atoms that are hidden from water.

5. Chaperone proteins can guide the folding of a newly synthesized polypeptide chain. The chaperones bind to newly synthesized or partially folded chains and help them to fold along the most energetically favorable pathway. The function of these chaperones requires ATP binding and hydrolysis.

6. Some chaperone proteins act as isolation chambers that help a polypeptide fold. In this case, the barrel of the chaperone provides an enclosed chamber in which a newly synthesized polypeptide chain can fold without the risk of aggregating with other polypeptides in the crowded conditions of the cytoplasm. This system also requires an input of energy from ATP hydrolysis, mainly for the association and subsequent dissociation of the cap that closes off the chamber.

7. Proteins are degraded by the proteasome. The structures depicted here were determined by x-ray crystallography. (A) This drawing shows a cut-away view of the central cylinder of the proteasome, with the active sites of the proteases indicated by red dots. (B) The structure of the entire proteasome, in which access to the central cylinder (yellow) is regulated by a stopper (blue) at each end. (B, from P.C.A. da Fonseca et al., Mol. Cell 46:54–66, 2012. With permission from Elsevier.)

8. Proteins marked by a polyubiquitin chain are degraded by the proteasome. Proteins in the stopper of a proteasome (blue) recognize proteins marked by a specific type of polyubiquitin chain (red ). The stopper unfolds the target protein and threads it into the proteasome’s central cylinder (yellow), which is lined with proteases that chop the protein to pieces. 

9. Many proteins require post-translational modifications to become fully functional. To be useful to the cell, a completed polypeptide must fold correctly into its three-dimensional conformation and then bind any required cofactors (red ) and protein partners—all via noncovalent bonding. Many proteins also require one or more covalent modifications to become active—or to be recruited to specific membranes or organelles (not shown). Although phosphorylation and glycosylation are the most common, more than 100 types of covalent modifications of proteins are known. 

10. Protein production in a eukaryotic cell requires many steps. The final concentration of each protein depends on the rate of each step depicted. Even after an mRNA and its corresponding protein have been produced, their concentrations can be regulated by degradation.