Collagen

Collagen, the most abundant protein in vertebrates, is an extracellular, inextensible fibrous protein that comprises the major protein component of such stress-bearing structures as bones, tendons, and ligaments. The objective of this exercise is to develop an understanding of the fibrous portion of collagen and to show how the different levels of protein structure come together and form a highly ordered and stable fiber. Collagen's properties of rigidity and inextensibility are due to this highly ordered structure. The part of collagen without structural order is not illustrated in this model. This part of the protein complex having a different amino acid composition, lysine and hydroxylysine are particularly important residues, is globular in nature and not as structurally organized. Lysine and hydroxylysine form covalent crosslinks in the protein complex, thereby adding strength and some flexibility to the fiber. This covalent crosslinking continues throughout life and produces a more rigid collagen and brittle bones in older adults. Go to Collagen Structure & Function for information on functions and disorders of collagen, and a link to assembly movies of the triple helix of types I and IV is available in the External Links section.

Structure of a Segment

A fiber segment is made up of 5 tropocollagens, each is shown in a . One limitation of this model of collagen segment is that instead of having flush cut ends as shown here, the ends of the tropocollagen in an actual fiber section would be . When the tropocollagens come together to form the fiber segment, they actually overlap one another in a staggered pattern. The presents of these staggered ends permit the tropocollagens from different segments to associate, and this associations result in the formation of a strong fiber. Add tropocollagens at a time to form the fiber section, , , , . View fiber segment as . Viewing the segment from the end one can see that without the side chains being displayed the center of the fiber is empty. Each contains 3 parallel peptide chains wrapped around one another to make a right-handed triple helix that is 87 Å long and ~10 Å in diameter. Tropocollagen displayed as only. The peptides making up the tropocollagen have a conformation which produces a . This helix has a rise which gives 3.3 residues/turn compared to 3.6 for the α helix. The shows that the psi and phi angles of the collagen helix are different from the α-helix. The two clusters shown here are outside of the area expected for an α-helix. Review where you would expect a cluster of α-helix residues to be located.

Primary Structure and Higher Levels of Structure

of the peptide in wireframe display. Identify the amino acids making up the peptide by resting the cursor on a residue and observing the name in the label (Stopping spin will make this easier.). Which three amino acids are present in the peptide in a reocurring pattern? Collagen is characterized by a distinctive repeating sequence: (Gly-X-Y)n where X is often Pro, Y is usually 5-hydroxyproline (Hyp), and n may be >300. The model (4CLG) being studied contains this of residues - Gly-Pro-Hyp. This sequence produces in the peptide chain a with 3.3 residues per turn and a pitch (rise per turn) of 10.0 Å. Looking down the axis of a tropocollagen displayed as wireframe, glycine can be seen of the triple helix. Proline and the hydroxyproline are on the of the triple helix. With the hydroxyproline being on the outside of the triple helix, its hydroxy groups can be involved in hydrogen bond formation as will be seen in the next section. The primary structure - Gly-Pro-Hyp - of the peptide determines these positions in the tropocollagen. The triple helix structure requires the close packing of the interior residues of the triple helix making only a small volume available for side chains in the interior of the tropocollagen. The consist of only a hydrogen (Realize that in this model the hydrogen on the α carbon is not displayed.), and therefore only glycine cam accommodate this close packing in the interior of the triple helix. , Gly:16 on each of three different chains, are close packed together. The gray atoms of the yellow and lime Gly are the α-carbons, and only a hydrogen could fit between the carbons and the atoms of the adjacent Gly. on each of the 3 chains are shown close packed to the three Gly (lime, cyan, yellow). Adding to the complex extends the close packing around the small glycines.

Maintainance Forces

Intra-tropocollagen attractions are primarily formed between the in the triple helix (tropocollagen); two such bonds are shown in this scene. In both examples the electron donating atom is a carbonyl oxygen of Pro in one peptide, and the hydrogen is part of a Gly imino group in the other peptide.

Hydrogen bonds are also an important inter-tropocollagen force which holds the tropocollagens together in the fiber segment. These hydrogen bonds involve the hydroxy groups of Hyp which is a residue on the outer surface of the triple helix (see above). This gives you a perspective for the one to follow, it highlights in spacefill the two peptide between which the hydrogen bond is formed. Notice that they make contact with each other in the middle of the strands, and the hydrogen bond, which will be shown next, is located at this point of contact. The consist of the oxygen of a carbonyl of a Hyp in a peptide of one tropocollagen and the hydroxyl hydrogen of a Hyp in a peptide of another tropocollagen. Two make contact at the ends of the fiber segment, and of course it is within these regions where the intra-tropocollagen attractions occur. One example shows a formed between a hydrogen of Hyp in one peptide and an oxygen of a Gly carbonyl in a second peptide. At the other end of the two tropocollages a donates its electrons to a Hyp hydroxyl hydrogen. Show the in the context of the six peptides of the two tropocollagens. The above examples of hydrogen bonding illustrate that Hyp plays a central role in maintaining the structures of both the tropocollagen and the collagen fiber.

Effect of a Mutation

Some forms of collagen contain Ala, and this form is illustrated with 1CAG, a 30-residue of sequence (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 (Ala displayed as large wireframe and colored as C O N). Viewing 1CAG from the side of the fiber shows that this model of collagen also has these residues in the same positions: is buried in the interior and is only partially visible, is positioned closer to the surface and is much more visible, is clearly visible as being on the surface, is a substitute for Gly so it is only partially visible. Using 1CAG to compare the packing around Ala to that around Gly shows that the is not as close as it is about the Gly.