Protein dna interaction
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S.Prasanth Kumar, S.Prasanth Kumar, BioinformaticianBioinformatician
Molecular Interaction
Protein-DNA InteractionProtein-DNA Interaction
S.Prasanth Kumar Dept. of Bioinformatics Applied Botany Centre (ABC) Gujarat University, Ahmedabad, INDIA
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DNA-Protein Binding
Specific binding of proteins to a wide variety of nucleicacids underlies all aspects of gene expression, includinggenome replication, repair, transcription and RNA metabolism.
Classical Examples:Bacterial restriction system, Transcriptional regulationDNA mismatch repair
Instance:PNA-DNA interaction
PNA
DNA
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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
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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
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Recognition Principles of DNA
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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
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DNA-Protein Contact Propensities
Luscombe et al 2001
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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
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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
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Spatial Interaction Patterns
N atom
O atomR
Kano & Sarai 2001
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Role of Solvated Cations in Charge Neutralization
Solvated Cations
Cations interact with Guanine of Major Groove to neutralize Charges
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Role of Methylation in Charge Neutralization
Used Methylphosphonate analogs in DNA duplexes
Methyl group neutralizes phosphate
Only phosphates in Minor groove
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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
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Shape Complementarity
Electrostatic potential prominent
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Protein’s Independent Binding Domains
LacI repressor
Known Domains
Zn finger
Leu zipper
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Electrostatic Patches
+ve
-ve
DNA binding protein Non-DNA binding protein
-ve
+ve
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Practical based on Protein-Protein-DNA Interaction DNA Interaction is followingis following
Special thanks to Wilma K. Olson for her illustrations presented in this lecture