Structural Features Forces and energetics of binding andor deformation

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Structural FeaturesForces and energetics of
binding and/or deformation
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B-DNA
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B-form (DNA, RNA)
A-form (RNA, DNA)
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Major Groove
Minor Groove
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Major Groove
Minor Groove
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Major Groove
Minor Groove
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Protein-Protein vs.
Protein-DNA
20n Polar nonpolar Chemical heterogeneity Rotame
rs Binding folding ?
20n Polar nonpolar Chemical heterogeneity Rotame
rs Binding folding ?
4n Polar ( nonpolar) Chemical
homogeneity Planar stacking Binding strain?
20n Polar ( nonpolar) Chemical
heterogeneity Rotamers Binding folding ?
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Protein DNA ProteinDNA complex
?G
?G ?H -T?S
Favorable ?H Unfavorable ?H Favorable
?S Unfavorable ?S Formation of H-Bonds Loss of
H-bonds (mostly with water) Release of bulk
solvent Reduction in of free species Electrostat
ic Contacts Unsatisfied buried charge Folding/o
rdering during binding van der Waals
packing Steric clash or buried cavities Molecula
r Strain (DNA)
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Enthalpic-entropic compensation DNA binding
events with similar affinities (usually ?G -10
kcal/mol) can be driven either by favorable ?H or
?S, both of which can vary widely from one system
to another. Allows DNA binding proteins that
extensively remodel DNA structure to display
similar free energies of binding and affinities
as proteins that dock to DNA with minimal
perturbation of structure.
(Figure from Linda Jen-Jacobson, 1997)
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Sequence specificity can be achieved by two
mechanisms
Direct and indirect readout
Direct Readout
Indirect Readout
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Sequence specificity can be achieved by two
mechanisms
Direct and indirect readout
Direct Readout
Indirect Readout
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Sequence-dependent energies of DNA
deformation Basepair propeller twisting G-C
1.5x greater than A-T Basepair unstacking can
vary by up to /- 10 kcal/mol per basepair step
depending on sequence C-G C-G C-G C-G G-C
A-T T-A C-G
14.59 kcal/mol
10.5 kcal/mol
9.8 kcal/mol
8.3 kcal/mol
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Sequence-specific ssDNA binding
Sequence non-specific ssDNA binding
Telomere-binding Protein
T4 Polynucleotide kinase
Oligosaccharide-binding (OB)Fold Multi-purpose
ssDNA binding functionality
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RNA Recognition of non-canonical
structure (loops, unpaired and flipped bases,
bulges)
tRNA-truB PsU synthetase complex
Ribosomal binding protein U1A