Structure of Nucleic Acids
Nucleotides and Nucleic Acids
Both DNA and RNA are known as nucleic acids. They have been given this name for the simple reason that they are made up of structures called nucleotides. Those nucleotides, themselves comprising a number of components, bond together to form the double-helix first discovered by the scientists James Watson and Francis Crick in 1956. This discovery won the two scientists the Nobel Prize. For now, when we discuss nucleic acids you should assume we are discussing DNA rather than RNA, unless otherwise specified.
A nucleotide consists of three things:
- A nitrogenous base, which can be either adenine, guanine, cytosine, or thymine (in the case of RNA, thymine is replaced by uracil).
- A five-carbon sugar, called deoxyribose because it is lacking an oxygen group on one of its carbons.
- One or more phosphate groups.
Nucleotides join together through phosphodiester linkages between the 5' and 3' carbon atoms to form nucleic acids. The 3' -OH of the sugar group forms a bond with one of the negatively charged oxygens of the phosphate group attached to the 5' carbon of another sugar. When many of these nucleotide subunits combine, the result is the large single-stranded polynucleotide or nucleic acid, DNA ()
If you look closely, you can see that the two sides of the nucleic acid strand shown above are different, resulting in polarity. At one end of the large molecule, the carbon group is unbound and at the other end, the -OH is unbound. These different ends are called the 5'- and 3'-ends, respectively.
The Helical Structure of DNA
shows a single strand of DNA. However, as stated earlier, DNA exists as a double-helix, meaning two strands of DNA bind together.
An important thing to remember about the structure of the DNA helix is that as a result of anti-parallel pairing, the nitrogen base groups face the inside of the helix while the sugar and phosphate groups face outward. The sugar and phosphate groups in the helix therefore make up the phosphate backbone of DNA. The backbone is highly negatively charged as a result of the phosphate groups.
The Importance of the Hydrogen Bond
Hydrogen bonding is essential to the three-dimensional structure of DNA. These bonds do not, however, contribute largely to the stability of the double helix. Hydrogen bonds are very weak interactions and the orientation of the bases must be just right for the interactions to take place. While the large number of hydrogen bonds present in a double helix of DNA leads to a cumulative effect of stability, it is the interactions gained through the stacking of the base pairs that leads to most of the helical stability.
Hydrogen bonding is most important for the specificity of the helix. Since the hydrogen bonds rely on strict patterns of hydrogen bond donors and acceptors, and because these structures must be in just the right spots, hydrogen bonding allows for only complementary strands to come together: A- T, and C-G. This complementary nature allows DNA to carry the information that it does.
Chargaff's rule states that the molar ratio of A to T and of G to C is almost always approximately equal in a DNA molecule. Chargaff's Rule is true as a result of the strict hydrogen bond forming rules in base pairing. For every G in a double-strand of DNA, there must be an accompanying complementary C, similarly, for each A, there is a complementary paired T.
DNA is a Right-Handed Helix
Each strand of DNA wraps around the other in a right-handed configuration. In other words, the helix spirals upwards to the right. One can test the handedness" of a helix using the right hand rule. If you extend your right hand with thumb pointing up and imagine you are grasping a DNA double helix, as you trace upwards around the helix with your fingers, your hand is moving up. In a left-handed helix, in order to have your hand move upwards with your thumb pointing up, you would need to use your left hand. DNA is always found in the right-handed configuration.
The Major and Minor Grooves
As a result of the double helical nature of DNA, the molecule has two asymmetric grooves. One groove is smaller than the other. This asymmetry is a result of the geometrical configuration of the bonds between the phosphate, sugar, and base groups that forces the base groups to attach at 120 degree angles instead of 180 degrees. The larger groove is called the major groove while the smaller one is called the minor groove.
Since the major and minor grooves expose the edges of the bases, the grooves can be used to tell the base sequence of a specific DNA molecule. The possibility for such recognition is critical, since proteins must be able to recognize specific DNA sequences on which to bind in order for the proper functions of the body and cell to be carried out. As you might expect, the major groove is more information rich than the minor groove. This fact makes the minor groove less ideal for protein binding.
Characteristics of the DNA Double-Helix
DNA will adopt two different forms of helices under different conditions--the B- and A-forms. These two forms differ in their helical twist, rise, pitch and number of base pairs per turn. The twist of a helix refers to the number of degrees of angular rotation needed to get from one base unit to another. In the B-form of helix, this is 36 degrees while in the A-form it is 33 degrees. Rise refers to the height change from one base pair to the next and is 3.4 angstroms in the B-form and 2.6 angstroms in the A-form. The pitch is the height change to get one full rotation (360 degrees) of the helix. This value is 34 angstroms in the B-form since there are ten base pairs per turn. In the A-form, this value is 28 angstroms since there are eleven base pairs per full turn.
Of the two forms, the B-form is far more common, existing under most physiological conditions. The A-form is only adopted by DNA under conditions of low humidity. RNA, however, generally adopts the A-form in situations where the major and minor grooves are closer to the same size and the base pairs are a bit tilted with respect to the helical axis.