Title

Mapping Quaternary Peptide Binding of PDZ Domains

Poster Number

19

Lead Author Major

Biochemistry

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

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Apr 25th, 10:00 AM Apr 25th, 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.