|Lecture Notes: 7 February
© R. Paselk 2006
3-D Structure of Proteins 3
Secondary Structure, cont.
Collagen strand: This is a specialized structure occurring in only a particular family of fibrous proteins. It does not occur in globular proteins that I am aware of.
- Collagen triple helix. Note repeating sequence of -(gly-x-y)- where x is usually proline and y is usually hydroxyproline. (Fig 4.36) [overheads: 11-8&10, S; 4-10 to 12]
Non-repetitive secondary elements: Proteins can also have non-repetitive secondary structures which consist of a few residues in a turn or loop. Among these are:
- Type I turns: Fig. 4.18, left [overhead 7.22, V&V] four amino acid residues in a 180° turn, usually H-bonded between the carbonyl O of the first residue and the amide N of the fourth. Proline is often the second residue. [overhead, 7-22 V&V]
- Type II turns: Fig. 4.18 [overhead 7.22, V&V] four amino acid residues in a 180° turn, usually H-bonded between the carbonyl O of the first residue and the amide N of the fourth. Glycine is most frequently the third residue and proline is often the second residue. [overhead, 7-22 V&V]
- A partial turn of a 310 helix. Short sections of this helix often occur at the ends of alpha-helixes as transitional elements.
The Tertiary structure describes the overall folding of a single covalent structure.
- Lysozyme model [overhead, model]
As the number of known protein structures increased additional patterns became obvious within the tertiary level of structure: Motifs & Domains.
Super Secondary structures (Motifs)
- Recall the two classical structures based on the beta-strand:
- Anti-parallel b-pleated sheet: strong, linear H-bonds spaced adjacent, then R grp, then single, then R grp, then adjacent etc. (Fig 4.15b) [overhead 7-17 V&V, 5.19 P]
- Parallel b-sheet: evenly spaced, but slanted H-bonds (less stable), (Fig 4.15a) [overhead 5.19 P]
Let's next look at some of the other more common motifs found in globular proteins (Fig 4.19 of your text):
- Hairpin - b-strand-short loop-b-strand
- b-meander - an anti-parallel beta sheet with short connecting loops
- aa motif - two successive alpha-helixes with slightly inclined axis to give better contact between side chains
- bab unit: alternate pattern of beta-strands and alpha-helixes
- Greek Key
Large proteins (>200 aa's) usually fold up in smaller pieces of 100-200 aa's called domains. Recall that we define a Domain as an independent folding region in a protein. Often defined by clefts in 3D structure giving globular elements connected by "hinges" (single strand segments connecting the domains). Domains have the advantages of speeding up the folding process (fold domains independently, then assemble resultant folded domains - effectively processing folding of domains in parallel). Another advantage of domain structure is that nature can take bits of DNA specifying particular domains with particular functions and assemble them in new combinations to get new activities (e.g. combine an ATP binding site and a sugar binding site to give a sugar phosphorylating protein).
Example: IgG , domains, exons and evolution. [overheads: IgG/proteins; 7.23 MvH]
- IgG made up of four independently synthesized proteins, 2 heavy chains with 4 domains each, and 2 light chains with 2 domains each.
- Domain types: b-meander [anti-parallel b-sheet], b-barrel. (Note that Motifs and Domains often use the same nomenclature, and indeed often overlap. Can in fact have Motif = Domain = Tertiary structure!)
- Domains correspond to exons of DNA (frequently, but not always the case)
- The domains are all apparently related through gene duplication in the remote past.
- The active site of IgG (2/IgG) is made up between two domains, one from a heavy chain and one from a light chain.
- When immune system is developing individual cells express single IgG molecules made from randomly expressed heavy and light chains.
In a similar manner we see that many enzymes have active sites created between two domains, often one domain binds one substrate while the second binds a second substrate.
Its as if these proteins were designed by taking "off-the-shelf" components, assembling them, and then over time (and generations) tuning the combination up.
Last modified 7 February 2007