Protein dna interaction


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Strategies of Protein DNA interaction

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Protein dna interaction

  1. 1. S.Prasanth Kumar, Bioinformatician Molecular Interaction Protein-DNA Interaction S.Prasanth Kumar Dept. of Bioinformatics Applied Botany Centre (ABC) Gujarat University, Ahmedabad, INDIA Sivakumar FOLLOW ME ON ACCESS MY RESOURCES IN SLIDESHARE prasanthperceptron CONTACT ME [email_address]
  2. 2. DNA-Protein Binding Specific binding of proteins to a wide variety of nucleic acids underlies all aspects of gene expression, including genome replication, repair, transcription and RNA metabolism. Classical Examples: Bacterial restriction system, Transcriptional regulation DNA mismatch repair Instance: PNA-DNA interaction PNA DNA
  3. 3. Mechanisms of DNA-Protein Binding Release of water molecules and ions DNA & Protein structure conformations Water at Interface : Helps in Electrostatic repulsions between like charges of protein and DNA Facilitates H bonding between protein and DNA Hence, water is important for binding
  4. 4. Recognition Principles of DNA Watson-Crick Rule Major Groove Edges Prominent HBA & HBD N atom O atom W Site in Wide Groove S Site in Small Groove
  5. 5. Recognition Principles of DNA
  6. 6. DNA-Protein Contact Propensities Protein-DNA Crystal Structures Select Non redundant structures Study Interaction Interaction with Bases Interaction with Sugar Interaction with Phosphate Backbone Interaction
  7. 7. DNA-Protein Contact Propensities Luscombe et al 2001
  8. 8. How Protein Recognizes its Site on DNA Protein uses SAA Protein uses +ve and/or polar residues Protein recognizes phosphate and base atoms Protein measures contact distance e.g. <3.4 Angstrom Protein converges to contact by folding mechanism
  9. 9. How Protein Recognizes its Site on DNA Other Structural Parameters H- bonded atoms found in tight clusters (next slide) van der Waals contacts of aa and bases are distant & dispersed Adenine
  10. 10. Spatial Interaction Patterns N atom O atom R Kano & Sarai 2001
  11. 11. Role of Solvated Cations in Charge Neutralization Solvated Cations Cations interact with Guanine of Major Groove to neutralize Charges
  12. 12. Role of Methylation in Charge Neutralization Used Methylphosphonate analogs in DNA duplexes Methyl group neutralizes phosphate Only phosphates in Minor groove
  13. 13. DNA Bending Strategy Excess charge on one side of DNA makes to bend towards neutralized regions Cations accumulated for phosphate neutralization at a region is the reason for DNA bending
  14. 14. Shape Complementarity Electrostatic potential prominent
  15. 15. Protein’s Independent Binding Domains LacI repressor Known Domains Zn finger Leu zipper
  16. 16. Electrostatic Patches +ve -ve DNA binding protein Non-DNA binding protein -ve +ve
  17. 17. Practical based on Protein-DNA Interaction is following Special thanks to Wilma K. Olson for her illustrations presented in this lecture