Mapping Quaternary Peptide Binding of PDZ Domains
Poster Number
19
Format
Poster Presentation
Faculty Mentor Name
Jerry Tsai
Faculty Mentor Department
Chemistry
Abstract/Artist Statement
PDZ domains are regulatory proteins that bind the C-terminal peptide of proteins, and many are involved in the development of cancer. Knowledge of the binding mechanism of PDZ domains would provide new avenues for cancer treatment. Using the knob-socket model to map out the quaternary packing surface topology allows a direct analysis of the residue groups important for peptide specificity and affinity to the PDZ domain. The PDZ domain includes 5 β- strands, 2 α-helices and 6 coils/turns and these were mapped based on the knob-socket model. In agreement with previous experimental analyses, the peptide S0 and S-2 positions directly interact with the PDZ domain, but the binding is more complex. Comparison between different PDZ domains and their respective peptides show that the S0 position packs primarily against the first coil, and the S-2 position packs into the second α-helix. These 2 positions on the peptide form β-sheet interactions with 2 positions on the second β-strand to provide a new interaction with the conserved Leu from the second α-helix. Similar β-sheet interactions between the peptide and the second β-strand provide another mode for specificity and affinity of PDZ domain binding. In another case, a residue from the peptide packs directly into a β-hairpin of the PDZ domain that increases affinity and specificity. These results clearly demonstrate the utility of knob-socket mapping of protein-peptide quaternary structure.
Location
DeRosa University Center, Ballroom
Start Date
25-4-2015 10:00 AM
End Date
25-4-2015 12:00 PM
Mapping Quaternary Peptide Binding of PDZ Domains
DeRosa University Center, Ballroom
PDZ domains are regulatory proteins that bind the C-terminal peptide of proteins, and many are involved in the development of cancer. Knowledge of the binding mechanism of PDZ domains would provide new avenues for cancer treatment. Using the knob-socket model to map out the quaternary packing surface topology allows a direct analysis of the residue groups important for peptide specificity and affinity to the PDZ domain. The PDZ domain includes 5 β- strands, 2 α-helices and 6 coils/turns and these were mapped based on the knob-socket model. In agreement with previous experimental analyses, the peptide S0 and S-2 positions directly interact with the PDZ domain, but the binding is more complex. Comparison between different PDZ domains and their respective peptides show that the S0 position packs primarily against the first coil, and the S-2 position packs into the second α-helix. These 2 positions on the peptide form β-sheet interactions with 2 positions on the second β-strand to provide a new interaction with the conserved Leu from the second α-helix. Similar β-sheet interactions between the peptide and the second β-strand provide another mode for specificity and affinity of PDZ domain binding. In another case, a residue from the peptide packs directly into a β-hairpin of the PDZ domain that increases affinity and specificity. These results clearly demonstrate the utility of knob-socket mapping of protein-peptide quaternary structure.