Chem 438 - Introductory Biochemistry - Spring 2013
Lecture illustrations from Moran text in [Brackets]
3-D Structure of Proteins, cont.
Last time looked at Primary structure (1°), Secondary structure (2°) and Tertiary structure (3°). Continuing:
- 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,
- Super secondary structure (motifs): defined associations
of secondary structural elements. (Characteristic bond type:
hydrogen & hydrophobic.)
- 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.)
The most frequent secondary structure is the right-handed -helix. [Figure 4.10 , pg 90]
- In this cylinder-like structure the amino acid residues curl around in a spring/rod-like structure.
- There is a rise/residue (movement along the axis) of 0.15 nm and a pitch (rise/turn) of 0.54 nm.
- There are 3.6 residues per turn and 13 atoms/H-bonded "ring" - this makes it a 3.613 helix.
- Very importantly, the H-bonds are nearly linear and therefore of near maximum strength. The side chains of the helix stick out from the sides. [Figure 4.11]
- The stability of the helix is determined in part by the side chains. Thus glycine allows too much rotational freedom to favor this structure, while very large or like charged side chains can also destabilize it.
- Note arrangement of residues in amphipathic helix. [Figure 4.12A & B, 4.13]
- As you might expect a proline residue stops a helix abruptly since proline' s angles are not accommodated in the helix.
The next secondary structural element is the -strand, which is seen in the supersecondary structures called parallel [Figure 4.16a]and anti-parallel -sheets. [Figure 4.16b]
- The beta strand is in a sense an abstract structure, since, unlike the -helix, a -strand does not exist alone, there is always another strand to make a sheet in the final structure.
- In the older literature beta-sheets are considered secondary structures, but they are more consistently considered super secondary with the current nomenclature.
- Beta strands are nearly fully extended, thus they have very little extensibility (stretch).
- Beta strands are stabilized by hydrogen bonding to adjacent -strands. Thus they are stabilized by inter-strand H-bonds whereas -helices are stabilized by intra-strand H-bonds.
- Side chains stick out perpendicular to sheet [Figure 4.17]
Aside: Fibrous proteins: alpha-keratin (hair etc., alpha-helix based), stretchy, breaking and remaking H-bonds; stretched alpha-keratin (parallel -pleated sheet), no longer stretchy, fully extended. "Permanent wave" breaking -S-S- bonds between adjacent -helix strands with thiol-reagent reducing agent, then rearrange hair and reoxidize with peroxide to lock new conformations in place.
- 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 4.40]
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. 4.19], left 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.
- Type II turns: [Fig. 4.19] 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.
- 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.
As the number of known protein structures increased additional patterns became obvious within the tertiary level of structure: Motifs & Domains.
Super Secondary structures (Motifs)
- Super secondary structure (motifs): defined associations of secondary structural elements. (Characteristic bond type: hydrogen & hydrophobic.)
Domains are independent folding regions within a protein. [Figure 4.21] The group/pattern of secondary structures forming a Domain's tertiary structure is called a Fold [some common folds: Figure 4.25]; example proteins with domains and folds: [Figure 4.24]. (Characteristic bond type: hydrophobic; others: hydrogen, ion-pair, van der Waals.) 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).
© R. A. Paselk 2010;
Last modified 11 February 2013