Bio 211 Into Molecular and Cell Biology Molecules of Life II
Lecture 5 “Proteins and Nucleic Acids”
Reading: Campbell Chap. 5 pp. 69-80.
In the last lecture, we looked at some of the molecules crucial to cells, including sugars and fats. This week we will continue by examining the structure and chemistry of proteins and nucleic acids.
Outline:
1. Protein primary structure
2. 3D structure of proteins
3. Nucleic acids
Proteins are important for almost everything cells do. Some important types of proteins are summarized in the following table (abbreviated Table 5.1).
Type of protein Function Examples
structural support keratin: hair, nails
collagen: tendons
storage store amino acids ovalbumin: egg white
transport carry substances hemoglobin: carrys O2
hormone coordination insulin: regulate blood sugar
receptor cell response acetyl choline receptor: nerve cell
contractile movement actin and myosin
defense protection antibodies
enzyme accelerate reactions trypsin: digestive enzyme
Humans may have one hundred thousand different proteins, each with a specific structure and function. The function of proteins depends on their three dimensional shape or conformation.
1. Protein primary structure
Proteins are long polymers made up of amino acids. A chain of amino acids is also called a polypeptide chain.
There are 20 kinds of amino acids that typically make up proteins. All amino acids contain at least two functional group, an amino group and a carboxyl group. They also usually contain some other functional group (sometimes designated as R groups).
Figure 5.15 summarizes the structure of the 20 amino acids in proteins.
The side chains in proteins can be organized based on the chemical properties of their R groups.
non-polar polar charged
glycine serine aspartic acid
alanine threonine glutamic acid
valine cysteine lysine
leucine tyrosine arginine
isoleucine asparagine histidine
methionine glutamine
phenylalanine
tryptophan
proline
non-polar side chains are hydrophobic
polar side chains are hydrophilic
other side chains have additional acidic or basic groups that tend to make the molecule be charged at neutral pH; they are also hydrophilic
Amino acids are linked together by peptide bonds to form proteins. Peptide bonds are formed by condensation (dehydration), see Fig. 5.16. The length of proteins can vary from a few residues (these are usually called peptides) to thousands of amino acids.
2. Three-dimensional conformation of proteins
The function of proteins depends on how they are folded, not just on the sequence of amino acids. We recognize four different levels of protein structure
a. primary structure: refers to the sequence of amino acids
b. secondary structure: refers to certain regions of the folded protein, alpha helix and pleated sheet.
c. tertiary structure: refers to the three-dimensional folding of the protein
d. quarternary structure: refers to proteins made of more than one polypeptide chain; how do these fit together in space?
The primary structure is the unique arrangement of amino acids in a protein. Fig. 5.18 shows the primary structure of the enzyme lysozyme. Lysozyme is a enzyme that can break down bacterial cell walls. There are 129 different amino acids in lysozyme and 20129 different ways those amino acids can be arranged. However the sequence of a protein is not left to chance, but is determined by an inherited gene.
The exact sequence of a protein can be determined in the laboratory. This is done by cleaving the protein into smaller fragments with protein-digesting enzymes and then determine the order of amino acids in each fragment. Fred Sanger was the first to sequence a protein, insulin, at Cambridge University in England in the early 1950’s.
Secondary structure refers to two types of regions that occur when a protein is folded, alpha helix and beta pleated sheet. Fig. 5.20 shows examples of these types of regions in a folded protein. Both of these regions are due to the formation of hydrogen bonds between regions of the protein, occuring in a regular repeat.
An alpha helix is a coiled region, like a corkscrew. The coil is held together by hydrogen bonds between every fourth amino acid.
A beta pleated sheet is formed in regions where the polypeptide chain folds back and forth. Hydrogen bonds between the parallel regions hold the structure together. Some fibrous proteins like silk have large regions folded into pleated sheet.
Tertiary structure refers to how a protein is folded in three dimensions. Many different kinds of bonds contribute to the tertiary structure. Although we can predict from the amino acid sequence where regions of a protein may form alpha helix or beta sheet, we don’t know many of the rules yet controlling protein folding.
Bonds that contribute to secondary structure (Figure 5.22)
hydrogen bond
disulfide bridge (covalent bond)
ionic bond
hydrophobic interaction
Quaternary structure only is defined for proteins with more than one polypeptide chain. It is the overall 3D structure of the entire protein. Fig. 5.23 shows the quaternary structures of two proteins, collagen and hemoglobin. Collagen is a tough fibrous protein that strengthens connective tissue (the tissue of tendons and ligaments). Collagen’s quaternary structure is a triple helix. Hemoglobin carries oxygen. Hemoglobin’s quaternary structure consists of 2 identical alpha subunits and two identical beta subunits.
Denaturation: The non-covalent bonds holding a protein in its correct conformation are weak and can be destroyed by heat, pH, and salt concentration. Sometimes these affects are reversible and the protein can resume its normal conformation once these are removed.
3. Nucleic acids
Nucleic acids are polymers of nucleotides that function in carrying and transmitting genetic information. There are two types of nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
DNA usually consists of two strands and carries the genes, the code to make proteins or RNAs. When cells divide, the strands separate and an exact replica is made and passed on to the daughter cells.
Information from DNA is transcribed into RNA (Figure 5.26) in the nucleus. The type of RNA known as “messenger RNA” contains the code to make the proteins. The decoding process (translation) takes place on cytoplasmic structures called ribosomes.
Nucleic acids are synthesized from building blocks called nucleotides. Nucleotides consist of three components, a 5 C sugar (ribose or deoxyribose), a nitrogen-containing base, and a phosphate (Figure 5.27).
The bases in DNA are of 4 types:
Purines contain two rings and include adenine (A) and guanine (G).
Pyrimidines contain one ring and include thymine (T) and cytosine (C)
In DNA, nucleotides are connected into long strands through their sugar and phosphate groups; these form the “sugar-phosphate” backbone. The bases extend toward the inside of the molecule.
The information in a gene is carried by the exact order that the bases occur on the DNA. So the sequence AACGGGCCC carries different information than the sequence TTTGCGCAT.
In double-stranded DNA, the sequence of bases are complementary on the two strands.
“A” pairs with “T” and “C” pairs with “G”
Thus the base sequence 5’ AACGGGCCC 3’ would be paired to the sequence:
3’ TTGCCCGGG 5’
The bases hold the strands together in the middle by hydrogen bonding. The sugar-phosphate backbones then wind around each other in a “double-helix”. The three dimensional structure of DNA was predicted by James Watson and Frances Crick in 1953, based on the X-ray crystallographic data of Rosalind Franklin.
Summary: Today we examined the structure and chemistry of two important macromolecules of cells, proteins and nucleic acids. Proteins are made up of a distinct sequence of amino acids that fold into a functional 3D structure. Nucleic acids carry the information that specifies the sequence the cell should use to make proteins. The nucleic acids DNA and RNA are made of nucleotides, which further consist of sugar, phosphate and nitrogenous bases.
In the coming lectures, we will move from a discussion of the molecules of cells to the processes that go on in cells. We will see that proteins, particularly enzymes have key roles to play in cellular reactions.
1