MCAT Biochemistry Review
Chapter 1: Amino Acids, Peptides, and Proteins
1.4 Primary and Secondary Protein Structure
Proteins are polypeptides that range from just a few amino acids in length up to thousands. They serve many functions in biological systems, such as enzymes, hormones, membrane pores and receptors, and elements of cell structure. Proteins are the main actors in cells; the genetic code, after all, is simply a recipe for making thousands of proteins.
Proteins have four levels of structure: primary (1°), secondary (2°), tertiary (3°), and quaternary (4°). In this section, we'll examine the first two; we'll discuss tertiary and quaternary structure in the next section.
The primary structure of a protein is the linear arrangement of amino acids coded in an organism's DNA. It's the sequence of amino acids, listed from the N-terminus, or amino end, to the C-terminus, or carboxyl end. So, for example, the first ten amino acids of the β-chain of hemoglobin are normally valine, histidine, leucine, threonine, proline, glutamate, glutamate, lysine, serine, and alanine. This is often abbreviated to a set of three-letter abbreviations, such as Val – His – Leu – Thr – Pro – Glu – Glu – Lys – Ser – Ala, or even as a series of one-letter abbreviations, VHLTPEEKSA. Primary structure is stabilized by the formation of covalent peptide bonds between adjacent amino acids.
The MCAT is unlikely to ask you questions that require you to memorize either the three-letter or one-letter abbreviations. You might see them in the context of a passage, though. More important, you definitely will not be expected to memorize the exact primary sequence of any protein!
The primary structure alone encodes all the information needed for folding at all of the higher structural levels; the secondary, tertiary, and quaternary structures a protein adopts are the most energetically favorable arrangements of the primary structure in a given environment. The primary structure of a protein can be determined by a laboratory technique called sequencing. This is most easily done using the DNA that coded for that protein, although it can also be done from the protein itself.
A protein's secondary structure is the local structure of neighboring amino acids. Secondary structures are primarily the result of hydrogen bonding between nearby amino acids. The two most common secondary structures are α-helices and β-pleated sheets. The key to the stability of both structures is the formation of intramolecular hydrogen bonds between different residues.
The primary structure of a protein is the order of its amino acids. The two main secondary structures are the α-helix and β-pleated sheet, which both result from hydrogen bonding.
The α-helix, shown in Figure 1.12, is a rodlike structure in which the peptide chain coils clockwise around a central axis. The helix is stabilized by intramolecular hydrogen bonds between a carbonyl oxygen atom and an amide hydrogen atom four residues down the chain. The side chains of the amino acids in the α-helical conformation point away from the helix core. The α-helix is an important component in the structure of keratin, a fibrous structural protein found in human skin, hair, and fingernails.
Figure 1.12. Hydrogen Bonding and Spatial Configuration of an α-Helix
In β-pleated sheets, which can be parallel or antiparallel, the peptide chains lie alongside one another, forming rows or strands held together by intramolecular hydrogen bonds between carbonyl oxygen atoms on one chain and amide hydrogen atoms in an adjacent chain, as shown in Figure 1.13. To accommodate as many hydrogen bonds as possible, the β-pleated sheets assume a pleated, or rippled, shape. The R groups of amino residues point above and below the plane of the β-pleated sheet. Fibroin, the primary protein component of silk fibers, is composed of β-pleated sheets.
Figure 1.13. Hydrogen Bonding and Spatial Configuration of a β-Pleated Sheet
Secondary Structures and Proline
Because of its rigid cyclic structure, proline will introduce a kink in the peptide chain when it is found in the middle of an α-helix. Proline residues are thus rarely found in α-helices, except in helices that cross the cell membrane. Similarly, it is rarely found in the middle of pleated sheets. On the other hand, proline is often found in the turns between the chains of a β-pleated sheet, and it is often found as the residue at the start of an α-helix.
MCAT Concept Check 1.4:
Before you move on, assess your understanding of the material with these questions.
1. What are the definitions of primary and secondary structure, and how do they differ in subtypes and the bonds that stabilize them?
Primary structure (1°)
Secondary structure (2°)
2. What role does proline serve in secondary structure?