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Folding in the polypeptide chain is restricted by the following criteria :
Due to restriction imposed by the amide bond rotation in polypeptides are allowed only about the N-C(alpha) and C(alpha)-C(carbonyl) bonds, as shown in the accompanying image :
The accompanying movie depicts an animation of one of the rotations around the N-C(alpha) bond for the ala-ala dipeptide.
Of the several possible secondary structures for polypeptides the most important are the alpha-helix and the beta-sheet. These two structures are the most common secondary structures observed in proteins.
Above we can view an ideal alpha-helix of alanine residues. The major stabilizing factor is that all possible intrachain hydrogen bonds are formed between the C=O and N-H groups in the backbone. The helical arrangement allows these hydrohgen bonds to be approximately linear.
allows for an interactive display of the helix structure.
In the beta pleated sheet structure shown below each amino acid residue is rotated by 180 degrees with respect to the preceeding one. If individual chains are then layered one on top of another linear hydrogen bonds can occur between adjacent chains. Beta sheets can occur as either :
allows for an interactive display of the beta pleated sheet structure.
Click here to view the Ramachandran diagram.
These proteins play major structural roles in animal cells and tissues. There are several distinct structural classes. They include the major proteins of skin and connective tissue and of animal fibers like hair, wool and silk.
Fibroin, as represented by the fibers spun by the silkworm, is typified by long regions of antiparallel beta-sheets running parallel to the fiber axis. The alteration of serine with either alanine or glycine residues allows the sheets to pack together in the arrangement shown.
Collagen is the most abundant single protein in most vertebrates. Collagen fibers are a major portion of tendons and an important constituent of skin. These fibers are built from triple helices of polypeptides rich in glycine and proline.
Globular proteins fold into structures called domains. A domain is a compact locally folded region of tertiary structure, and different domains are connected by polypeptide strands. Different domain types are often associated with different protein functions. Several domain varieties are common to many globular proteins :
Aldolase, which catalyzes the hydrolysis of Fructose-1,6-biphosphate, is a clear example of a twisted beta-sheet surrounded by alpha-helices.
Adenylate Kinase, which catalyzes ADP-ATP conversion, ia also a good example of a mixed alpha-helix and beta-sheet domain.
Beta-sheets are often twisted or wrapped into barrel structures.Bacteriochlorophyll Protease is a dramatic example of such a beta-sheet domain, with the beta-sheet barrel housing the porphyrin reaction center and the bound Mg2+ cation.
Quaternary structure refers to proteins formed by the association of protein subunits into multisubunit structures. Hemoglobin is a tetramer, comprised of four polypeptide subunits, two of one type (alpha) and two of another (beta). Thus hemoglobin exhibits quaternary strcture, with the subunits held together by non-covalent interactions. Each subunit has a primary, secondary and tertiary structure somewhat similar to that of myoglobin with each containing a heme group with a single oxygen-binding site.
Protein-Protein interactions result from the action of noncovalent forces at complementary protein surfaces. The following example involves the interaction of an enzyme inhibitor, bovine pancreatic trypsin inhibitor (BPTI), with the protein trypsin to form a tight, specific complex. In the following animation the BPTI protein (6kD) first complexes with the zymogen trysinogen only to form a loose, weakly bound complex. The zymogen is then cleaved to form active trypsin which binds with the inhibitor BPTI to form a tightly bound complex.
Denaturation is the loss of a protein's or DNA's three dimensional structure. The "normal" three dimensional structure is called the native state. Denaturation is physiological -- structures ought not to be too stable. Double stranded DNA must come apart to replicate and for RNA synthesis. Proteins must be degraded under certain circumstances. To terminate their biological action (e.g., enzymes). To release amino acids (e.g., for gluconeogenesis in starvation). Loss of native structure must involve disruption of factors responsible for its stabilization. These factors are:
Note that no break in the polymer chain (disruption of primary structure) is involved in denaturation. Denaturing agents disrupt stabilizing factors. A movie detailing the denaturation (i.e. unfolding) of a protein can be viewed.
