Globular proteins have a 3D molecular structure that has a shape that is anywhere from a sphere to a cigar. Usually the structure of a globular protein is divided into three or four levels. The primary structure is simply the sequence of amino acids forming the peptide chain. The peptide chain can be folded in an ordered and repetitive fashion, and the structures with ordered and repetitive conformations are called secondary structures. Helices, β-sheets and turns are three important types of secondary structures. Turns are classified as a secondary structure even though their structures are ordered but not repetitive. The tertiary structure is the overall 3D structure of a globular protein and is produced by folding the helices and sheets upon themselves with turns and loops forming the folds. Non-covalent molecular attractions are important forces in maintaining the folded conformation of a globular protein. For the most part, these attractions are between the atoms of the side chains but can be between the side chains and a bound ligand. Hydrogen bonds between back bone atoms are important in maintaining secondary structures, and those between side chains are involved in maintaining the tertiary structure. Examples of finding and visualizing both types in globular proteins are at hydrogen bonds. The attractive forces of salt bridges are important in maintaining some tertiary structures, but they also can be involved in the binding of ligands. The Disulfide bond is the one type of covalent bond that can play an important role in maintaining the tertiary structure as well as connecting two or more peptide chains together. Links to sites having structures that illustrate disulfide bonds are at Cystine. Some globular proteins have a quaternary structure, and it is formed when two or more globular protein molecules (monomer) join together and form a multimeric unit. Hemoglobin is a good example of a protein that has a quarternary structure.
The tertiary structure of many globular proteins can be characterized by the number of layers of peptide backbone which are present and the attractive forces which are generated by these layers. Other important characteristics in the absence of backbone layers are the presence of disulfice bonds, of chelated metal ions or of intrinsically unstructured segments . The objective of this page is to introduce the tertiary structures of globular proteins by illustrating these characteristics of globular proteins.
Layers of Backbone Present in the Structure
Layers of backbone in the core of the structure is a feature that many, but not all, globular proteins have. The number of layers and their location vary for different proteins, but in all of these proteins the hydrophobic forces between the layers play a major role in maintaining the tertiary structure.
The ribbons representing the backbones show the two layers of α-helices. The are shown in ball and stick with one layer colored green and the other cyan. Notice that these side chains are mostly located between the layers and that few are on the exterior of the molecule. View the between the two layers. The between the layers are only on the edges. The are now ball & stick, and they tend to be on the surface of the molecule where they can associate with . More clearly see polar groups on the surface by so that axis of helix aligns with z-axis, compare this scene with a similarly aligned display of the hydrophobic side chains.
Load the and rotate it to observe the three layers. Hopefully you positioned it similar to these . Show the hydrophobic residues in . With the CyanDark layer being the middle layer most of its side chains are nonpolar. The hydrophobic side chains are again nearly all located between the layers. Toggling spin off and rotating the structure to align the helical axis with the z-axis gives an even better view of this effect. Display the polar residues in . The polar side chains are almost exclusively on the surface of the molecule, and therefore the middle CyanDark layer has very few polar side chains.
Load the . The circular layers formed by the β-sheet barrel (yellow) and α-helix barrel are clearly seen in this view, giving what would appear to be two layers. shows that hydrophobic residues occupy the central circular cavity as well as the space between the two circular layers. With this being the case one could say that the isomerase had four layers of backbone. . As the structure rotates one can see that most of the polar residues are on the surface, but there are few within the central cavity and between the two circular layers. The β-sheet of the barrel is parallel because after forming a strand of the sheet the peptide chain loops out, forms an α-helix and then loops back to form another strand of the sheet running in the same direction as the previous strand and, thereby, making the sheet parallel.
Load . Rotate the structure and attempt to identify the five layers. The five layers are in colors Brown through Red. Display; it is not as obvious as with the previous proteins, but as the structure rotates one can see that most of the spheres are in the interior between the layers. Looking at the , as it rotates one can observe more spheres on the edges of the structure than were seen in the previous scene.
Other examples of protein having the characteristic of layered backbones will be divided into three categories - predominately α-helix, predominately β-sheets and mixed α-helix and β-sheets.
The peptides in this class have a high contain of α-helix and because of the loops and turns which are present the α-helical strands will be antiparallel with respect to their adjacent strands.
Mixed helices and β-Sheets
Disulfide bonds and metal ion chelates can stabilize the tertiary structure in the absence of well organized layers which generate hydrophobic attractions. Some proteins are small in size and therefore do not have large amounts of backbone that can be organized into layers. Others have significant backbone, but the layers are not well organized and therefore are non-stabilizing. The attractions formed by metal ions chelates or disulfide bonds in these proteins are as important or more so than the hydrophobic interactions of the organized layers. Examples of both types of bonds will be given.
Some proteins or peptide segments are intrinsically disordered (unstructured). Whether a complete protein or a protein segment since they are disordered, they can not be crystallized for x-ray crystallographic study. However, when these peptides or peptide segments bind to other proteins they become ordered segments, and can be crystallized along with the binding protein for x-ray crystallographic study. When these peptides bind to other proteins, since their conformations are extended and not compact, the binding occurs over relatively large surface areas of the binding proteins. Examples given below illustrate the extended conformations of the peptide segments as well as the large binding surface. When viewing the unstructured peptides as unbound segments, realize that the conformation which is being displayed is not a disordered conformation but is the conformation of the bound segments with the structure of the binding protein being hidden. If the peptides or peptide fragments were actually free and unbound, since they are unordered, the individual molecules would have a range of conformations and not just one.
Intrinsically Unstructured Proteins