Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431	Biochemistry	Fall 2007
Lecture Notes: 19 September	© R. Paselk 2007
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3-D Structure of Proteins 3

Tertiary Structures

The Tertiary structure describes the overall folding of a single covalent structure. With small proteins (< 200 aa residues) the overall structure is generally characterized by an overall tertiary folding with particular secondary structural segments to give particular motifs. Four small proteins are illustrated in your text:

• Myoglobin (text Figure 4-16) is a 153 residue globular protein in the globin family. Eight alpha helices form its single domain (myoglobin fold) tertiary structure; about 80% alpha helix (high for globular proteins). Interior almost exclusively hydrophobic residues, with water excluded from interior. Surface has mix of hydrophobic and hydrophilic residues, with ionizable groups on surface.
  • X-ray Diffraction determination of protein structure.
    • Review x-ray diffraction learned in Chem 109 (Bragg equation)
    • Note the each crystal point now becomes many points, each with its own "reflecting" plane.
    • Rotation to determine relative locations in three space results in thousands of reflections
    • Need to add heavy metals to act as "beacons" to locate positions in absolute space, and need to do a couple of times isomorphically (without altering the proteins structure - isomorphic replacements).

    Finally use Fourier transforms to convert angles and intensities of reflections to 3-D map of protein.

  Myoglobin functions to store and facilitate the diffusion of oxygen in muscle. Oxygen binds to a heme {Fe (II)-protoporphyrin IX} prosthetic grp. Four of irons six ligands are to heme nitrogens, with a fifth to a histidine nitrogen. The final ligand bond goes to oxygen. Breathing motions (see below) are necessary to allow the exchange of oxygen, since the heme is in a closed pocket.
• Lysozyme model (text Figure 4-18b, model)
• Cytochrome c (text Figure 4-18)
• Ribonuclease (text Figure 4-18)

Note that of the four, myoglobin, an intracellular protein, does not have dissulfide bonds, whereas the other three, all extracellular proteins, have dissulfide bonds to stabilize them in their relatively harsh environment.

Note also the presence of alpha-helices and beta-sheets in these proteins (text Table 4-2) to give motifs.

• In looking at these motifs note that they tend to be made of layers allowing non-polar side chains to be buried so that hydrophobic forces stabilize them (text Figure 4-20a). Note that when -helices and -sheets occur together they are generally in different layers.
• Note that peptides segements nearby in the primary sequence generally stack adjacent to each other in the tertiary folded structure.
  • We also find that the folding follows relatively simple patterns, with no crossovers or knots. (text Figure 4-20b)
• -sheets are most stable, and thus most commonly found, when the individual segments have a slight right-handed twist. This leads to complex structures such as the -barrel etc. (text Figure 4-20d)

As the number of known protein structures increased, and larger proteins were determined, additional patterns became obvious within the tertiary level of structure: Motifs, which we introduced last time, & Domains.

Secondary structural elements have become the basis of classifications systems of protein types based on four classes:

1. All alpha
2. All beta
3. alpha/beta (have alternating alpha and beta structures, such as in the beta-alpha-beta motif)
4. alpha + beta (local clusters of alpha and beta in same chain with each cluster consisting of contiguous primary structure).

1. All alpha (text Figure 4-22a)
2. All beta (text Figure 4-22b)
3. alpha/beta (text Figure 4-22c)
4. alpha + beta (text Figure 4-22d)

Unlike the two classification laevels above, the next level is based on evolutionary relationships. Folds/Motifs are often more highly conserved than sequences, and so are used along with sequences to trace relatedness among molecules and thus organisms.

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Last modified 21 September 2007