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A very simplistic approach to explain B-DNA structure variations during the formation of protein-DNA complexes.
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Helix Structure And Molecular Recognition By B-
DNAA heap of paradoxes
Characteristics of B-DNA
• It is a right handed helix.• Angle of helical twist per turn is 35.9°.• BP/turn = 10.5• Diameter = 20 Å• The major groove, is 22 Å wide and the other,
the minor groove, is 12 Å wide.
Questions that arise…
• Do local helical structures of DNA depend on local base pair sequence ?
• To map the DNA structural deviations, which sample should we use? Aq. solution or DNA crystals ?
• If GC base pairs make DNA more stable then why does it have a lot of AT BPs ?
Dodecamer Decade
• CGCxxxxxxGCG• All the possible nucleotides with this sequence
were synthesized, crystallized and subjected to X-ray crystallography.
• To chalk out rules for helical twist, roll angle, rise, slide, propeller twist etc. on the basis of data thus obtained.
• This data could be used to distinguish different forms and conformations of DNA.
Calladine’s Rules
• It was realized that value of a helix parameter could be affected by preceding or following steps.
• It was discovered that B-DNA decamers, when crystallized, would behave a very long, repetitive helix.
• It exhibited different local parameters in different crystalline environment.
• What is going on ? Did DNA not have a fixed structure ?
• Are X-ray crystallography data accidents produced by local crystal packing forces ?
• Is DNA duplex just a shapeless mass of Brownian spaghetti ?
Sequence Based Differential Deformability
• The deviation range exhibited by a particular helical parameter depends on the sequence.• But the exact conformation depends
on the crystalline environment, or the environment that an approaching protein creates.
Molecular Properties: inferences
• Sugar pucker is C2’-endo. But it deviates and goes as far as C4’-exo. On the other hand A-DNA sugar pucker is more clustered around C3’-endo.
• This shows that B-DNA is more malleable than other structural alternatives. Due to less rigidity, it is more suitable for involvement in molecular recognition process.
Contd…
• AT pairs show more variability in propeller twist. (Double H-bond)
• Similarly, minor grooves width is more variable in regions of successive AT base pairs.
• Mean twist angle is 36°. But varies from 20° to 55°.
• Bending of B-DNA duplex are caused by Roll. (Tilt is rather unfavorable).
Sequence Factor
• Pyrimidine = Y, Purine = R• Y-R steps• R-Y / R-R steps
Correlation (Local roll/twist/slide/tilt)
• Heterogeneous step ending in A, display negative correlation between slide and roll, twist and roll; and positive correlation between slide and twist.
• In Y-R steps, large slide or twist do not favor a large positive roll. (except C-G)
• R-Y steps prefer negative values of slide and twist.• The correlation plots have proved out to be
similar to those from crystallography analysis.
Protein-DNA complexesFour Classes (Describe): • HTH proteins• Zn-binding proteins• bZIP, bHLH• Others
CAP-DNA
Conclusions
Bending• Bends are the result of ROLL (mostly).• Bend for a protein can be achieved by (kinks,
slow progression).• Role of major groove and minor groove.• Y-R steps are most prone to roll/slide bending.• R-R steps are very stiff, especially A-A.
Base Occurrence
• A-A step is most common of all (16%).• 55% of these are poly-A runs.• Preference for A-A is a consequence of natural
selection for a stabilizing structural element.• By contrast G-G base pairs are rare and less
compatible with complexes involving Sequence Reading.
• [These are all probabilistic rules, not hueristic.]