Copyright © 2000-2011 Mark Brandt, Ph.D. 42 Examples of Protein Structures Protein types Proteins fall into three general classes, based on their overall three-dimensional structure and on their functional role: fibrous, membrane, and globular. Fibrous proteins Fibrous proteins tend to be long, narrow molecules. Fibrous proteins are used to construct macroscopic structures, especially structures outside of cells. Fibrous proteins tend to have a structural role, although some have more active functions as well. Examples: The protein α-keratin is used to form hair, nails, and skin. α-Keratin is a coiled-coil of α-helices ~300 residues long (corresponding to about 450 Å in length). α-Keratin is formed from two α-helices wrapped around one another (the backbone shown below is of a coiled-coil protein from PDB ID 3Q0X; this portion of the protein probably resembles the keratin coiled-coil structure)), and two of those structures wrapped around each other. Thus the keratin molecule contains a total of four intertwined helices. The helices in α-keratin are slightly distorted in order to allow the coiled-coil, but otherwise are formed from torsion angles similar to those present in normal α-helices. The approximate Φ / Ψ pair for the keratin helix is –64° / –42° compared to a normal α-helix of –57° / –47°. The position of the keratin helices are maintained in their relative locations by hydrogen bonds and disulfide bonds formed between side-chains of the helical chains. Hair and nail α-keratin molecules have a higher disulfide bond content than the form of keratin found in skin, and are tougher as a result. High humidity allows facile rearrangement of hydrogen bonds, and can therefore allow the keratin molecules in hair to change their relative positions somewhat. Individuals with curly hair frequently find the degree of curling depends on the humidity; they also usually find that hair shaped while wet tends to retain its structure upon drying. A “permanent” results from reduction of the disulfide bonds between the chains, followed by shaping the hair, and by then oxidizing the free sulfhydryl groups to form new disulfide bonds that hold the hair in the new shape. Smaller coiled-coil structures are also found at the interaction interface betweenCopyright © 2000-2011 Mark Brandt, Ph.D. 43 some types of proteins that form less permanent complexes than keratin (especially in some transcription factors such as leucine zipper proteins). The multiple types of collagen together comprise the most common animal protein (about 25% of the protein in animals is some form of collagen). Collagen is a triple helix formed from three polypeptide chains. The individual polypeptides form helices that are much more extended than an α-helix. A collagen helix contains 3.3 residues/turn compared to 3.6 residues/turn, but has a rise of 10 Å/turn, compared to 5.4 Å for an α-helix. An α-helix has a rise per residue of 1.5 Å; in contrast, a collagen helix has a rise of 3 Å per residue, and is therefore nearly as extended a structure as a β-sheet (3.5 Å/residue). The extended collagen helix is the result of its Φ / Ψ pair of –51° / 153°. The Φ angle is thus close to that of the α-helix, but the Ψ angle is quite different, and is close to the maximal extension angle (180°). The collagen triple helix has three of these extended helices wrapped around one another.10 The collagen triple helix is ~14 Å in diameter. Each chain in the collagen triple helix is ~1000 residues long. The collagen molecule is therefore about 3000 Å = 0.3 µm long ([1000/3.3 residue/turn]•10 Å). In collagen, the polypeptides have the typical sequence (Gly-X-Y)n. The X residues are frequently proline while the Y residues are frequently hydroxyproline or hydroxylysine. Glycine fits in the center of triple helix (it is the only residue that is small enough to do so). Proline readily adopts the Φ / Ψ angles required by the triple helix. Note the proline rings in the strands shown above. In collagen, the helices are held in register by several factors. One is hydrogen bonding formed using hydroxyproline residues. The hydroxyl group is added to the proline residues following the synthesis of the collagen molecule in a vitamin C-dependent reaction. Some of the symptoms of scurvy (vitamin C deficiency) are due to inhibition of proline hydroxylation in collagen. Another factor that stabilizes the collagen structure is the result of covalent cross links formed between lysine, hydroxylysine, and histidine residues within the protein.11 10 The drawing of collagen was created in VMD from PDB ID 3ADM; the structure was determined using trimers of a 27-residue artificial model peptide rather than a full-length collagen molecule. 11 Since collagen molecules are much shorter than the macroscopic structures such as tendons and ligaments that are produced largely from collagen, it is apparent that the larger structures require interactions between collagen molecules. Some of these interactions are also mediated by side chain hydrogen bonding and other links. GlyHydroxyProSerProGlyProGlyProProCopyright © 2000-2011 Mark Brandt, Ph.D. 44 Membrane proteins Membrane proteins comprise a unique class of proteins. For membrane proteins, a significant region of the protein must be stable in a hydrophobic environment. This is typically achieved by having non-polar side-chains on specific surface regions of the protein. Because of this exposed hydrophobic surface, and because many membrane proteins are destabilized by removal from the membrane, most membrane proteins are difficult to work with. As a result, structural information is available for only a relatively small number of these proteins, although new techniques have allowed three-dimensional structure determination for increasing numbers of membrane proteins in the last few years. An example of a membrane protein is cytochrome c oxidase. Cytochrome c oxidase is one of the more important membrane proteins: it is the protein that donates electrons to oxygen in the electron transport chain. Cytochrome c oxidase is