|Lecture Notes: 17 September
© R. Paselk 2008
- Now that we have looked at peptide bond formation, we next want to look at the structure of this bond and the sequence of amino acid residues (primary structures) of proteins. (Note that "residue" refers to the remainder of a molecule after it is incorporated into a polymer.)
- The peptide bond is formed with the elimination of water, giving a planar bond between the carboxyl carbon and the amino nitrogen. (text Figure 4-2b) This is due to the partial double bond character on the amide/peptide bond as seen in the shorter bond length (0.133 nm vs. 0.146 nm). (text Figure 4-2b) This bond is nearly always trans in proteins due to steric interactions of the amide hydrogen and oxygen, except for proline.
3-D Structure of Proteins
Overview: Proteins are commonly large (MW > 6,000), globular molecules serving many functions.
Proteins are complex systems - difficult to understand at a fundamental structural level. Thus we search for patterns using normal perceptual tools: regularity, clustering, cleavage/separation/emptiness.
We are then able to discern alpha helices, beta sheets, beta turns, and "random" regions. 310 helical regions show up with computer searches. None of these is necessarily more or less random than others, they are simply easier or more difficult for us to perceive as ordered. They exist through our rationalization. Often structural elements also appear to serve a functional role, thou this is through our dissection of the molecular machine.
Look at theoretical possibilities resulting from the available bond angles around the peptide bond system
- Most peptide bonds are trans because of reduced steric hindrance. Most exceptions are with proline which has nearly equal hindrance in both cis and trans [overhead 5.8 P]
(text Figure 4-7.b)
- Any rotation in the peptide chain will therefore take place around the two bonds of the alpha carbon, referred to as the phi and psi bonds. There are a restricted number of angles which these bonds can achieve (text Figure 4-2c,d) [overhead V&V 7.6]. Of course the range of angles will be further reduced due to side chains.
- If we assume hard spherical atoms with van der Waals radii, we can determine the accessible phi and psi angles. This procedure was followed by Ramachandran to produce the Ramachandran plot, an example is seen in text Figure 4-3.
- There are only a few regions of possible angles available to the alpha carbon bonds as shown on this plot. (text Figure 4.3)
- Note that the common secondary structures, the alpha helix, the beta strand, and the collagen triple helix all occur in these regions. (text Figure 4-8a)
- Of course real atoms are somewhat compressible and real bonds can bend a little, so we might wonder how this plot stacks up to reality. A study of the distribution of conformation angles of a thousand amino acid residues in eight proteins as determined by x-ray diffraction showed that most of the values do indeed fall in the predicted regions. Most of the residues outside of these regions are glycines, with the least restriction. A study of pyruvate kinase shows a similar distribution as seen in text Figure 4-8b - note that glycines are not shown.
Let's go back and look at overall shape and interpret it. Look for substructures that recur in various molecules. Perhaps we see a globule is made of subglobules. Look closer and we see alpha helices and beta structures. Finally we can discern aa residues.
In order to understand and categorize their organization, protein structure has been divided into four hierarchical levels and a couple of sublevels:
- Primary structure (1°) : the linear order or sequence of peptide bonded amino acid residues, beginning at the N-terminus. (Characteristic bond type: covalent.)
- Secondary structure (2°): the steric relations of residues nearby in the primary structure which give rise to local regularities of conformation. These structures are maintained by hydrogen bonds between peptide bond carbonyl oxygens and amide hydrogens. The major secondary structural elements are the alpha helix and the beta strand. (Characteristic bond type: hydrogen.)
- Super secondary structure (motifs): defined associations of secondary structural elements. (Characteristic bond type: hydrogen & hydrophobic.)
- Tertiary structure (3°): the steric relations of residues distant in the primary sequence; the overall folding pattern of a single covalently linked molecule. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals, disulfide.)
- Domains: independent folding regions within a protein. The group/pattern of secondary structures forming a Domain's tertiary structure is called a Fold. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals.)
- Quarternary structure (4°): the association of two or more independent proteins via non-covalent forces to give a multimeric protein. The individual peptide units of this protein are referred to as subunits, and they may be identical or different from one another. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals.)
Last modified 17 September 2008