Thursday, 3 April 2014

SHADOW OF DNA part-2

The most common DNA structure in solution is the B-DNA. Under conditions of applied force or twists in the DNA, or under low hydration conditions, it can adopt several helical conformations, referred to as the A-DNA, Z-DNA, S-DNA...


Shown in picture above are three crystallized states of DNA, the A-DNA (left), B-DNA (middle) and Z-DNA (right). The A-form crystallizes under low hydration conditions and is not normally found for DNA in the cell. It is, however, the structure adopted by double-stranded regions in RNA as well as the transient double-helix between DNA and RNA during transcription.  Both A- and B-DNA are right-handed helices whereas Z-DNA is a left-handed helix and is commonly found in regions of DNA that have an alternating purine-pyrimidine (e.g. 5'-CGCGCGCG-3' or 5'-CGCGCATGC-3') sequences. The table below summarizes some of the major differences.
                                    A-DNA                                B-DNA                                Z-DNA
                             Right-handed helix                    Right-handed                      Left-handed
                                Short and broad                     Long and thin                    Longer and thinner
Helix Diameter                25.5A                                  23.7A                                    18.4A
Rise / base-pair                 2.3A                                    3.4A                                      3.8A
Base-pair / helical turn       ~ 11                                    ~ 10                                        ~ 12
Helix pitch                            25A                                    34A                                        47A
Tilt of the bases                    20 deg                               -1 deg                                   -9 deg

The ball-and-stick representation shown above can be misleading because it suggests that there is empty space between the two strands and between the base-pair stacks. Another representation is the filled space representation in which each of the atoms are shown as a ball of radius representative of its Van der waals radius. The picture below shows this view for the 3 DNA structures shown above.

Here, the B-DNA is on the left and the A-DNA is in the middle. The blue and white atoms are the sugar-phosphate backbone atoms, the red are G-C base-pairs and the yellow are A-T base-pairs. The B-DNA picture shows very clearly the 'grooves' in between the backbones that also spiral around the DNA structure; the grooves in B-DNA come in two sizes, the minor groove and the major groove.
A DNA molecule is not a rigid, static structure as x-ray diffraction pictures might suggest, and the crystallographic parameters shown above are average parameters. In reality, each of these structures are under constant thermal fluctuations, which result in local twisting, stretching, bending, and unwinding of the double-strands. Also, certain sequences lead to permanent bends or kinks in the direction of the helix. These local (sequence-specific) fluctuations are essential for the recognition of specific binding sites along the DNA molecule where proteins involved in replication, transcription, regulation of gene expression, or DNA-damage repair can bind. 

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