Biochem Project: Molecular basis of DNAProtein interactions

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Biochem Project Molecular basis of DNA-Protein
interactions

• Instructor Dr. Rob Coalson
• By Jian
  Zhang

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Introduction

• Protein DNA-binding protein
• Try to assess general rules that govern amino
  acid-base (DNA) recognition based on the
  protein-DNA complex structures in the PDB

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1. Hydrogen bonds

• Possible binding sides of DNA base pairs

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• Protein can bind the DNA through the base, sugar,
  and the phosphate group
• Hydrogen bonds with phosphate are not specific,
  but with great importance in stabilizing the
  protein-DNA complexes
• Guanine exposes the greatest number of potential
  hydrogen-bonding atoms on the base edge(4
  positions)
• The polar and charged residues of amino acids
  play a central role
• Arg gt Lys gt Ser gt Thr Asn and Gln
• Acidic residues are used sparingly Asp and Glu
• Only Gly makes a significant number of
  interaction
• Few interactions are produced by hydrophobic
  residues

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Distribution of single hydrogen bonds with
DNA-base
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• Favored amino acid-base hydrogen bonds
• Arg and Lys --- G, Asp and Glu --- A, Ser
  and His --- G
• 80 of Ser and Thrs interactions are with
  the DNA backbone
• Hydrogen bond geometries
• Single 36.9
• Bidentate 33.8 ( two or more hydrogen
  bonds are made with a base or base pair)
• Complex 34.1 ( a protein residue binds
  more than one step simultaneously)

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Example Bidentate interaction with Arg
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2. Van der waals contacts

• Comprise 64.9 of all protein-DNA interactions
• Interactions with the DNA backbone ( sugar and
  phosphate) are most prominent
• Interactions with the phosphate group dominate
  due to their high exposure on the DNA surface
• TgtAgtGgtC
• Arg, Thr, Phe, Ile, His, Cys

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• Phe and His may have ring stacking interactions
  with the base ring
• Cys in coordinating proteins has a high
  propensity to contact the DNA backbone
• Glu, Ala, Leu, and Asp are less favored
• Glu and Asp electrostatic interactions with
  DNA
• Ala and Leu shortness of their side chains

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3. Water mediated bonds

• Nearly as common as direct hydrogen bonds
• 14.9 of all protein-DNA interactions
• 70 are with the DNA backbone, mostly phosphate
  group
• Interactions with purine are common than with
  pyrimidine
• Polar and charged amino acids are frequently
  used Arg, Lys, Asp, Glu, Ser and Thr

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Summery
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Example structure of Nucleosome
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Reference

• N.M. Luscombe et al, Nucl. Acid Res 29, 2860-2874
  (2001).
• Luger et al, Nature 389, 251-260 (1997)