Biochemistry 462a – Proteins: Secondary Structure
Reading - Chapter 6
Practice problems - Chapter 6 - 1,2; Proteins extra problems
Levels of Protein Organization
· The function of a protein can only be understood in terms of its structure. The three dimensional structures of many proteins have been determined and from these structures a few general principles can be derived. Protein structure is discussed in terms of
o Primary Structure is the amino acid sequence of its polypeptide chain(s). Every protein has a unique amino acid sequence.
o Secondary Structure is the spatial arrangement of the polypeptide backbone, ignoring the conformation of the sidechains.
o Tertiary Structure is the three dimensional structure of the entire polypeptide.
o Quaternary Structure refers to the three dimensional structure of proteins that are composed of two or more polypeptide chains, called subunits.
Secondary Structure
· Recall that peptide bond has partial double bond character that forces the OCNH atoms of the polypeptide backbone to be planar.· Thus, the only degrees of freedom for rotation in the polypeptide backbone are around the bonds to the Ca carbon - phi (f) or psi (y).
· However, there are significant limitations as to which angles of f and y can be used due to steric clashes between atoms. /
A Ramachandran Plot shows those regions of f and y where there are no steric conflicts. /
· For proteins, there are two major regions. In one the polypeptide chain adopts a b-strand conformation and in the other a a-helix conformation.
Secondary Structural Elements
· Proteins are organized with the hydrophobic sidechains in the interior and the hydrophilic side chains on the surface.
· Because the main chain peptide bond elements, C=O and N-H, are polar, placing them in the hydrophobic interior of a protein could create a major problem.
· This problem is solved by the formation of hydrogen bonds between the amide protons and carbonyl oxygens of the peptide bonds in the main chain.
· These hydrogen bonds cause the main chain to adopt regular secondary structures called a-helices and b-sheets.
The a-helix
· In the a-helix, intrachain hydrogen bonds are formed between the peptide bond elements 4 residues apart in the primary sequence.
· The peptide bond has a dipole moment /· Because all the hydrogen bonds in an a-helix are oriented along the helix axis, all the peptide bond units are also aligned in the same orientation along the helix axis.
· Because the peptide bond has a dipole moment arising from the polarity of the NH and C=O groups (see above), the helix itself has a Dipole Moment that runs the length of the helix with the amino terminal end of the helix carrying a partial positive charge and the carboxyl terminal a partial negative charge.
· The helix dipole moment plays an important role in binding charged ligands to proteins, as we shall see later. /
b-sheets
· In the case of b-sheet two or more b- strands are held together by interchain hydrogen bonds.
/ If the strands are oriented such that the N® C directions are the same, the sheet is called a parallel b-sheet. In this drawing the alpha carbons are red/ If the strands are oriented such that the N® C directions are opposite, the sheet is called an antiparallel b-sheet. In this drawing the alpha carbons are red.
Loops and Turns
· Most proteins contain combinations of a-helices and b-sheets, which are connected by loops.
· Loops have irregular lengths and shapes and are on the surface of the protein.
· The elements of the loop do not usually form hydrogen bonds to each other, but do form hydrogen bonds to water.
· Loop regions that connect two antiparallel b-strands are called hairpin loops or turns.· Here are two examples of a b-turn involving four residues - only the backbone chain is shown for clarity.
· Note how the turn is stabilized by a hydrogen bond between C=O of residue 1 and the H-N of residue 4.
· Proline is often involved in turns and also breaks a-helices because the planar sidechain cannot be accommodated in the helix. Bends and turns most often occur on the surface of proteins. /
Schematic Conventions in Representing Secondary Structural Elements
· This Chime routine provides a closer look (convention). /
Simple Motifs
· Secondary structural elements are connected to form simple motifs.
Filamentous Proteins
· There are a few proteins that form long filaments. In such proteins the structure is defined by secondary structures.
· Collagen - About one quarter of all of the protein in the body is collagen. Collagen is a major structural protein, forming the tendons and sheets that support the skin and internal organs. Bones and teeth are made by adding mineral crystals to collagen. Collagen is composed of three chains wound together in a triple helix. Each chain is over 1400 amino acids long and consists of a repeating sequence of three amino acids. Every third amino acid is glycine, a small amino acid that fits perfectly in the interior of the triple helix. Many of the remaining positions in the chain contain proline and a modified version of proline, hydroxyproline. We wouldn't expect proline to be this common, because it forms a kink in the polypeptide chain that is difficult to accommodate in typical globular proteins. But, as you can see in Chime script below it seems that proline is just the right shape for the collagen triple helix. Hydroxyproline, which is critical for collagen stability, is created by modifying prolines after the collagen chain is synthesized. The reaction requires vitamin C to assist in the addition of oxygen. We cannot make vitamin C and a vitamin C deficiency slows the production of hydroxyproline and stops the construction of new collagen, ultimately causing scurvy. Collagen from animals is a familiar ingredient for cooking - gelatin.
· In silk the protein chains are extended b-sheets.
2