User:R. Jeremy Johnson/Folding Synthesis: Difference between revisions
New page: == '''Introduction''' == Ribonuclease A has been the subject of Nobel Prizes on Protein Folding and Solid Phase Peptide Synthesis . The observation of ribonuclease folding helped Christian... |
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== '''Protein Folding''' == | == '''Protein Folding''' == | ||
[[Image:Proteopedia final 2d.png|thumb|280px|left|Residues important to the proper folding of RNase A. Locations of internal residues Pro-114, Pro-117, Cys-58, and Cys-72 are highlighted and labeled.]] | |||
Interatomic interactions, delegated by the amino acid sequence, are responsible for formation of a protein's 3D structure [http://en.wikipedia.org/wiki/Protein_folding]. Several of these interactions have been identified by the use of site directed mutagenesis to wildtype RNase A and subsequent comparison of the crystal structure to the wildtype. Although RNase A has 105 possible disulfide bond pairings, only one set of four bonds occurs. This unique observation leads to the "thermodynamic hypothesis", that a protein's native state is determined by the thermodynamic favorability of the whole system; thus the tertiary structure must be predetermined by intramolecular interactions within the amino acid sequence. Since thermodynamic stability of a protein is affected by the environment's temperature, pH, and ionic strength, among other factors, the protein structure can only exist under physiological conditions. Today, the correlation between the amino acid sequence and the tertiary structure of RNase A continues to serve as a model for protein folding. Among the most important attributes of this model are noncovalent interactions, proline conformation, and disulfide bonding. | Interatomic interactions, delegated by the amino acid sequence, are responsible for formation of a protein's 3D structure [http://en.wikipedia.org/wiki/Protein_folding]. Several of these interactions have been identified by the use of site directed mutagenesis to wildtype RNase A and subsequent comparison of the crystal structure to the wildtype. Although RNase A has 105 possible disulfide bond pairings, only one set of four bonds occurs. This unique observation leads to the "thermodynamic hypothesis", that a protein's native state is determined by the thermodynamic favorability of the whole system; thus the tertiary structure must be predetermined by intramolecular interactions within the amino acid sequence. Since thermodynamic stability of a protein is affected by the environment's temperature, pH, and ionic strength, among other factors, the protein structure can only exist under physiological conditions. Today, the correlation between the amino acid sequence and the tertiary structure of RNase A continues to serve as a model for protein folding. Among the most important attributes of this model are noncovalent interactions, proline conformation, and disulfide bonding. | ||
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Another important role of proline residues is their involvement in β turns. β turns are 180° turns commonly found in globular proteins to allow for a compact structure by connecting the ends of adjacent antiparallel β sheets [http://en.wikipedia.org/wiki/Beta_sheet]. The turn consists of a sequence of four amino acid residues. The carbonyl of the first amino acid hydrogen bonds with the amino group of the fourth amino acid. Proline is involved in β turns because it is small, flexible, and assumes a ''cis'' conformation, all attributes that allow for formation of a turn. In RNase A both Pro93 and Pro114 are involved in β turns. Proline residues are important to protein folding because their ability to form a favorable ''cis'' conformation allows for thermodynamic favorability of β turn formation. With β turns, amino acids can fold back on themselves allowing the protein to reside in a compact, globular structure. | Another important role of proline residues is their involvement in β turns. β turns are 180° turns commonly found in globular proteins to allow for a compact structure by connecting the ends of adjacent antiparallel β sheets [http://en.wikipedia.org/wiki/Beta_sheet]. The turn consists of a sequence of four amino acid residues. The carbonyl of the first amino acid hydrogen bonds with the amino group of the fourth amino acid. Proline is involved in β turns because it is small, flexible, and assumes a ''cis'' conformation, all attributes that allow for formation of a turn. In RNase A both Pro93 and Pro114 are involved in β turns. Proline residues are important to protein folding because their ability to form a favorable ''cis'' conformation allows for thermodynamic favorability of β turn formation. With β turns, amino acids can fold back on themselves allowing the protein to reside in a compact, globular structure. | ||
==='''Disulfide Bonds'''=== | ==='''Disulfide Bonds'''=== | ||