Protein Tertiary and Quaternary Structures: -Fibrous Proteins Are Adapted for a Structural Function

α-Keratin, collagen, and silk fibroin nicely illustrate the relationship between protein structure and biological function (Table 4–1). Fibrous proteins share properties that give strength and/or flexibility to the structures in which they occur. In each case, the fundamental structural unit is a simple repeating element of secondary structure. All fibrous proteins are insoluble in water, a property conferred by a high concentration of hydrophobic amino acid residues both in the interior of the protein and on its surface. These hydrophobic sur faces are largely buried by packing many similar polypeptide chains together to form elaborate supramolecular complexes. The underlying structural simplicity of fibrous proteins makes them particularly useful for illustrating some of the fundamental principles of protein structure discussed above. α-Keratin The α-keratins have evolved for strength. Found in mammals, these proteins constitute almost the entire dry weight of hair, wool, nails, claws, quills, horns, hooves, and much of the outer layer of skin. The-keratins are part of a broader family of proteins called intermediate filament (IF) proteins. Other IF proteins are found in the cytoskeletons of animal cells. All IF proteins have a structural function and share structural features exemplified by the α-keratins. The α-keratin helix is a right-handed α helix, the same helix found in many other proteins. Francis Crick and Linus Pauling in the early 1950s independently suggested that the helices of keratin were arranged as a coiled coil. Two strands of -keratin, oriented in parallel (with their amino termini at the same end), are wrapped about each other to form a supertwisted coiled coil. The supertwisting amplifies the strength of the overall structure, just as strands are twisted to make a strong rope (Fig. 4–11). The twisting of the axis of an α helix to form a coiled coil explains the discrepancy between the 5.4 Å per turn predicted for an α helix by Pauling and Corey and the 5.15 to 5.2 Å repeating structure observed in the x-ray diffraction of hair (p. 120). The helical path of the supertwists is left-handed, opposite in sense to the α helix. The surfaces where the two helices touch are made up of hydrophobic amino acid residues, their R groups meshed together in a regular interlocking pat tern. This permits a close packing of the polypeptide chains within the left-handed supertwist. Not surprisingly, α-keratin is rich in the hydrophobic residues Ala, Val, Leu, Ile, Met, and Phe. An individual polypeptide in the -keratin coiled coil has a relatively simple tertiary structure, dominated by an -helical secondary structure with its helical axis twisted in a left-handed superhelix. The intertwining of the two -helical polypeptides is an example of quater nary structure. Coiled coils of this type are common structural elements in filamentous proteins and in the muscle protein myosin (see Fig. 5–29). The quaternary structure of -keratin can be quite complex. Many coiled coils can be assembled into large supramolecular complexes, such as the arrangement of -keratin to form the intermediate filament of hair (Fig. 4–11b).

FIGURE 4–11 Structure of hair. (a) Hair -keratin is an elongated helix with somewhat thicker elements near the amino and carboxyl termini. Pairs of these helices are interwound in a left-handed sense to form two-chain coiled coils. These then combine in higher-order structures called protofilaments and protofibrils. About four protofibrils—32 strands of -keratin altogether—combine to form an intermediate filament. The individual two-chain coiled coils in the various substructures also appear to be interwound, but the handedness of the interwinding and other structural details are unknown. (b) A hair is an array of many -keratin filaments, made up of the substructures shown in (a).

The strength of fibrous proteins is enhanced by co valent cross-links between polypeptide chains within the multihelical “ropes” and between adjacent chains in a supramolecular assembly. In -keratins, the cross-links stabilizing quaternary structure are disulfide bonds (Box 4–2). In the hardest and toughest -keratins, such as those of rhinoceros horn, up to 18% of the residues are cysteines involved in disulfide bonds. Collagen Like the -keratins, collagen has evolved to provide strength. It is found in connective tissue such as tendons, cartilage, the organic matrix of bone, and the cornea of the eye. The collagen helix is a unique secondary structure quite distinct from the helix. It is left-handed and has three amino acid residues per turn (Fig. 4–12). Collagen is also a coiled coil, but one with distinct tertiary and quaternary structures: three separate polypeptides, called chains (not to be con fused with helices), are supertwisted about each other (Fig. 4–12c). The superhelical twisting is right-handed in collagen, opposite in sense to the left-handed helix of the chains. There are many types of vertebrate collagen. Typically they contain about 35% Gly, 11% Ala, and 21% Pro and 4-Hyp (4-hydroxyproline, an uncommon amino acid; see Fig. 3–8a). The food product gelatin is derived

FIGURE 4–12 Structure of collagen. (Derived from PDB ID 1CGD.) (a) The chain of collagen has a repeating secondary structure unique to this protein. The repeating tripeptide sequence Gly–X–Pro or Gly–X–4-Hyp adopts a left-handed helical structure with three residues per turn. The repeating sequence used to generate this model is Gly–Pro–4-Hyp. (b) Space-filling model of the same chain. (c) Three of these helices (shown here in gray, blue, and purple) wrap around one another with a right-handed twist. (d) The three-stranded colla gen superhelix shown from one end, in a ball-and-stick representation. Gly residues are shown in red. Glycine, because of its small size, is required at the tight junction where the three chains are in contact. The balls in this illustration do not represent the van der Waals radii of the individual atoms. The center of the three-stranded superhelix is not hollow, as it appears here, but is very tightly packed.

from collagen; it has little nutritional value as a protein, because collagen is extremely low in many amino acids that are essential in the human diet. The unusual amino acid content of collagen is related to structural constraints unique to the collagen helix. The amino acid sequence in collagen is generally a repeating tripeptide unit, Gly–X–Y, where X is often Pro, and Y is often 4-Hyp. Only Gly residues can be accommodated at the very tight junctions between the individual α chains (Fig. 4–12d); The Pro and 4-Hyp residues permit the sharp twisting of the collagen helix. The amino acid sequence and the supertwisted quaternary structure of collagen allow a very close packing of its three polypep tides. 4-Hydroxyproline has a special role in the structure of collagen—and in human history (Box 4–3). The tight wrapping of the chains in the collagen triple helix provides tensile strength greater than that

FIGURE 4–13 Structure of collagen fibrils. Collagen (Mr 300,000) is a rod-shaped molecule, about 3,000 Å long and only 15 Å thick. Its three helically intertwined chains may have different sequences, but each has about 1,000 amino acid residues. Collagen fibrils are made up of collagen molecules aligned in a staggered fashion and cross linked for strength. The specific alignment and degree of cross-linking vary with the tissue and produce characteristic cross-striations in an electron micrograph. In the example shown here, alignment of the head groups of every fourth molecule produces striations 640 Å apart.

of a steel wire of equal cross section. Collagen fibrils (Fig. 4–13) are supramolecular assemblies consisting of triple-helical collagen molecules (sometimes referred to as tropocollagen molecules) associated in a variety of ways to provide different degrees of tensile strength. The chains of collagen molecules and the collagen molecules of fibrils are cross-linked by unusual types of co valent bonds involving Lys, HyLys (5-hydroxylysine; see Fig. 3–8a), or His residues that are present at a few of the X and Y positions in collagens. These links create uncommon amino acid residues such as dehydrohy droxylysinonorleucine. The increasingly rigid and brittle character of aging connective tissue results from ac cumulated covalent cross-links in collagen fibrils.

FIGURE 4–14 Structure of silk. The fibers used to make silk cloth or a spider web are made up of the protein fibroin. (a) Fibroin consists of layers of antiparallel β sheets rich in Ala (purple) and Gly (yellow) residues. The small side chains interdigitate and allow close packing of each layered sheet, as shown in this side view. (b) Strands of fibroin (blue) emerge from the spinnerets of a spider in this colorized electron micrograph.

A typical mammal has more than 30 structural variants of collagen, particular to certain tissues and each somewhat different in sequence and function. Some human genetic defects in collagen structure il lustrate the close relationship between amino acid sequence and three-dimensional structure in this protein. Osteogenesis imperfecta is characterized by abnormal bone formation in babies; Ehlers-Danlos syndrome is characterized by loose joints. Both conditions can be lethal, and both result from the substitution of an amino acid residue with a larger R group (such as Cys or Ser) for a single Gly residue in each chain (a different Gly residue in each disorder). These single-residue substitutions have a catastrophic effect on collagen function because they disrupt the Gly–X–Y repeat that gives collagen its unique helical structure. Given its role in the collagen triple helix (Fig. 4–12d), Gly cannot be re placed by another amino acid residue without substantial deleterious effects on collagen structure.

Silk Fibroin, the protein of silk, is produced by insects and spiders. Its polypeptide chains are predominantly in the β conformation. Fibroin is rich in Ala and Gly residues, permitting a close packing of sheets and an interlocking arrangement of R groups (Fig. 4–14). The overall structure is stabilized by extensive hydro gen bonding between all peptide linkages in the polypeptides of each sheet and by the optimization of van der Waals interactions between sheets. Silk does not stretch, because the β conformation is already highly extended (Fig. 4–7; see also Fig. 4–15). However, the structure is flexible because the sheets are held together by numerous weak interactions rather than by covalent bonds such as the disulfide bonds in α-keratins.

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مواضيع ذات صلة

Protein Secondary Structure:- Common Secondary Structures Have Characteristic Bond Angles and Amino Acid Content

Protein Secondary Structure:- β Turns Are Common in Proteins

Protein Secondary Structure:- Amino Acid Sequence Affects α Helix Stability

Overview of Protein Structure:- The Peptide Bond Is Rigid and Planar

Overview of Protein Structure:- A Protein’s Conformation Is Stabilized Largely by Weak Interactions

Overview of Protein Structure:- The Peptide Bond Is Rigid and Planar

Overview of Protein Structure:- A Protein’s Conformation Is Stabilized Largely by Weak Interactions

Protein Sequences and Evolution:- Protein Sequences Can Elucidate the History of Life on Earth

The Covalent Structure of Proteins:- Amino Acid Sequences Provide Important Biochemical Information

The Covalent Structure of Proteins:- Small Peptides and Proteins Can Be Chemically Synthesized

The Covalent Structure of Proteins:- Amino Acid Sequences Can Also Be Deduced by Other Methods

The Covalent Structure of Proteins:-Large Proteins Must Be Sequenced in Smaller Segments