Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Proteins
Structure of Fibrous Proteins

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Fig. 11.1.

Fibrous Proteins are proteins characterized by a highly elongated shape. Due to the inherent rigidity or elasticity of these proteins, they frequently perform structural Functions in living organisms.

The conformation of the polypeptide chain in most fibrous Proteins can be classified into one of Three types of regular Secondary Structure: the Collagen helix, the ß-sheet found in many types of silk, and the a-helical structure characteristic of a-Keratins and Tropomyosin.

COLLAGEN, the most abundant mammalian protein, forms the structural basis of tendons, bones, Skin, Teeth, and Cartilage. The structural unit of a collagen fiber is the tropocollagen molecule, which consists of three polypeptide chains, each containing approximately 1000 amino acid residues. Depending on the function of the collagen, these polypeptide chains are either identical or possess very similar sequences.

The Amino Acid Composition of collagen is unusual. First, approximately one-third of all residues are Glycine, and second, There is a high proportion of Proline residues. Furthermore, collagen contains Two Amino Acids rarely found in other proteins: hydroxyproline and hydroxylysine. The side chains of these amino acids contain a hydroxyl (—OH) group attached to a carbon atom in place of a hydrogen atom. Hydroxylation is carried out by specific Enzymes after proline or Lysine has been incorporated into the collagen polypeptide chain.

The Amino Acid Sequence of the major portion of the collagen chain is characterized by regularly repeating Gly—X—Y units, where X and Y can be any amino acid residues. Proline (Pro) is most frequently found in the X position, whereas hydroxyproline (Hyp) predominantly occupies the Y position. A typical segment of a collagen sequence is structured as follows:

—Gly—Pro—Hyp—Gly—Pro—Met—Gly—Pro—Hyp—Gly—Leu—Ala—

This regular sequence adopts a conformation known as the collagen helix. In the segments comprising the first 16 residues at the N-terminus and the last 25 residues at the C-terminus of the collagen polypeptide chain, this regularity in the alternation of amino acid residues is absent. These segments, termed telopeptides, have a conformation distinct from the collagen helix. A single collagen peptide chain forms a helix in which the axial distance between amino acid residues is 0.29 nm, with slightly fewer than three residues per helical turn. The helix is left-handed in the sense that if the fingers of the left hand are positioned to trace the path G1—X2—Y3—G4, the thumb will point in the direction from the N-terminus to the C-terminus. No Hydrogen Bonds are formed between the backbone atoms of a single polypeptide. Nevertheless, this conformation (which is significantly more extended than the a-helix, where the residue spacing is 0.15 nm) is favored for a polypeptide chain containing the bulky pyrrolidine rings of proline and hydroxyproline residues.

The term triple collagen helix is used to describe The structure of the regular portion of the tropocollagen molecule. In the triple collagen helix, three single collagen chains are arranged parallel to one another and wound around each other to form a rope-like coiled structure. This twisting is made possible by the right-handed supercoiling of the left-handed single collagen helices, which can be observed by the resulting Displacement of the a-chain when transitioning from G1 to G4 (where G1 and G4 are glycine residues located at the first and fourth positions, respectively). A single collagen chain contains approximately 1000 residues, and the length of the tropocollagen molecule is about 300 nm.

Glycine is the only residue that can fit near the axis of the triple helix, as the available space there is insufficient to accommodate any larger side chain. There are approximately three residues per turn of the single chain, which necessitates a glycine residue at every third position of The amino acid sequence. The side chains of the X and Y residues project outward from the axis of the triple helix and can be quite bulky. In the triple helix, hydrogen bonds exist between the >N—H group of each internal glycine residue and the >C=O group of another chain.

Collagen assembly begins with the synthesis of procollagen molecules in fibroblasts. Procollagen is a precursor of collagen that features additional peptide extensions at both the N- and C-termini. Within fibroblasts, procollagen molecules spontaneously fold into triple helices, with the C-termini of the three chains linked together by Disulfide Bonds. In this form, the triple helices are secreted from The Cell and subsequently converted into tropocollagen molecules upon the Enzymatic Cleavage of the procollagen extension Peptides by procollagen peptidase.

A microfibril is an aggregate of parallel-aligned tropocollagen molecules, each longitudinally displaced relative to its neighbor by 67 nm (a shift known as the D-period or D-spacing). In addition, a gap of 40 nm exists between the C-terminus of one molecule and the N-terminus of the next. Microfibrils associate with one another to form a fibril, and several fibrils group together to form a collagen fiber (Fig. 11.2). Collagen fibers are stabilized by covalent cross-links between polypeptide chains, rendering them highly tensile-resistant and exceptionally strong, as any noticeable elongation of the fibers requires the rupture of these cross-links.

Fig. 11.2.

Connective Tissues in structures such as bones, tendons, and cartilage typically possess a complex architecture consisting of collagen and other molecules, predominantly Inorganic Components. As noted, in tendons, calcium is deposited in the gaps between adjacent collagen molecules. A similar situation occurs in bones.

Silk predominantly exhibits an antiparallel ß-sheet structure, in which the ß-chains run parallel to the fiber axis. In many varieties of silk, the distance between adjacent ß-sheets alternates between 0.35 nm and 0.57 nm. The amino acid sequence is largely a repetition of the Gly—Ala—Gly—Ala—Gly—Ser unit. The side chains of all Ala and Res residues are situated on one side of the ß-sheet, while the hydrogen atoms of the glycine residues project from the other side. The ß-sheets are packed in such a way that identical surfaces contact one another. The spacing between layers contacting via their "glycine" surfaces is 0.35 nm, whereas the spacing between surfaces featuring protruding Ala and Ser residues is 0.57 nm. Silk fibers are largely inextensible because any significant elongation would result in the rupture of covalent bonds within the polypeptide chain. Some degree of extensibility is nevertheless observed and may be attributed to local irregularities in the amino acid sequence, such as the introduction of residues with bulky side groups like Tyr, Arg, Asp, and Glu. At these sites, the ß-Structure is disrupted, and the polypeptide chain adopts a non-regular conformation that can be stretched without breaking covalent bonds.

KERATIN is a vital protein component of Hair, wool, Nails, claws, and feathers. In one of its forms, known as a-keratin, the underlying STRUCTURE OF THE polypeptide chain is a right-handed a-helix. The hypothesis that keratin possesses an a-helical conformation was proposed by Pauling and Corey to account for the X-Ray Diffraction data of keratin fibers obtained by Astbury in the 1930s. However, the pitch of the keratin helix is 0.51 nm, which is smaller than the 0.54 nm pitch of a standard a-helix. This discrepancy arises because two, and possibly three, chains are coiled around each other to form a coiled-coil structure termed a protofibril. Eleven protofibrils assemble to form a microfibril, and a bundle of microfibrils constitutes a keratin fiber. a-Keratins are readily extensible because stretching disrupts hydrogen bonds, allowing The polypeptide chains to transition into a ß-conformation. This process generates interchain Hydrogen bonds and leads to The formation of ß-sheets. Keratins with this structure are referred to as ß-keratins.

TROPOMYOSIN is a protein found in Muscles (Chapter 36) that consists of two intertwined a-helices, structurally analogous to the arrangement found in a-keratin.