Structural and energetic determinants of tyrosylprotein sulfotransferase sulfating specificity

ORAL

Abstract

Tyrosine sulfation is a type of post-translational modification which is catalyzed by the enzyme tyrosylprotein sulfotransferase (TPST). There is no well-defined sequence motif for tyrosine sulfation, and the selection criteria for a sequence undergoing sulfation remain elusive. We estimated the binding affinity of peptides with tyrosines to TPST and attempted to differentiate the sulfated and non-sulfated sequences. We find that sequences which undergo sulfation in general have stronger binding affinity. Even though simple binding affinity score can satisfactorily differentiate the two sets of sequences, we found that the predictions are further improved after including energy costs associated with local unfolding. These include costs for melting secondary structures and solvent exposing the peptide residues. Our results suggest that in addition to binding affinity, the thermodynamic availability of the peptide is important for sulfation specificity. Our method is expected to be useful in predicting potential sulfation sites. Since we use simple physics-based method, we expect it to be transferable to other TPST variants, and also other post-translational modification systems.

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Authors

  • Praveen Nedumpully-Govindan

    Clemson University, Clemson, SC

  • Brad Cox

    North Carolnia State University, Vanderbilt University, University of South Carolina, University of Virginia, Francis Marion Univ, Oak Ridge National Laboratory, Massachusetts Institute of Technology, Florida International University, Georgia College, JINR, Tsinghua University, LBNL, GANIL, Austin Peay State University, Lehigh University, University of Pardubice, Universit\'e de Rennes, Austin Peay State University Department of Physics and Astronomy, Oak Ridge National Laboratory, Oak Ridge TN 37831, American Superconductor Corp., Westborough MA 01581, University of North Georgia, Dahlonega GA 30597, Florida State University, Ecole Polytechnique, Space Telescope Science Institute, Fermi National Accelerator Lab, National Optical Astronomy Observatory, Austin Peay State Univerity, North Carolna State University, Florida Intl Univ, University of North Georgia, Clemson University, Clemson Univ, Vanderbilt University/ORNL, Vanderbilt University/Univ. of Kentucky, College of William and Mary, Louisiana State University, Presbyterian College, North Carolina State Univ, Department of Physics, Virginia Tech, Mathematical Institute, University of Oxford, Virginia Tech University, Hollins University, University of Tennessee Space Institute, Davidson College, University of Tennessee, American Superconductor Corporation, University of South Alabama, North Carolina State University, James Madison University, Lousiana State University, Korea Electrotechnology Research Institute, Changwon Korea

  • Brad Cox

    North Carolnia State University, Vanderbilt University, University of South Carolina, University of Virginia, Francis Marion Univ, Oak Ridge National Laboratory, Massachusetts Institute of Technology, Florida International University, Georgia College, JINR, Tsinghua University, LBNL, GANIL, Austin Peay State University, Lehigh University, University of Pardubice, Universit\'e de Rennes, Austin Peay State University Department of Physics and Astronomy, Oak Ridge National Laboratory, Oak Ridge TN 37831, American Superconductor Corp., Westborough MA 01581, University of North Georgia, Dahlonega GA 30597, Florida State University, Ecole Polytechnique, Space Telescope Science Institute, Fermi National Accelerator Lab, National Optical Astronomy Observatory, Austin Peay State Univerity, North Carolna State University, Florida Intl Univ, University of North Georgia, Clemson University, Clemson Univ, Vanderbilt University/ORNL, Vanderbilt University/Univ. of Kentucky, College of William and Mary, Louisiana State University, Presbyterian College, North Carolina State Univ, Department of Physics, Virginia Tech, Mathematical Institute, University of Oxford, Virginia Tech University, Hollins University, University of Tennessee Space Institute, Davidson College, University of Tennessee, American Superconductor Corporation, University of South Alabama, North Carolina State University, James Madison University, Lousiana State University, Korea Electrotechnology Research Institute, Changwon Korea

  • Brad Cox

    North Carolnia State University, Vanderbilt University, University of South Carolina, University of Virginia, Francis Marion Univ, Oak Ridge National Laboratory, Massachusetts Institute of Technology, Florida International University, Georgia College, JINR, Tsinghua University, LBNL, GANIL, Austin Peay State University, Lehigh University, University of Pardubice, Universit\'e de Rennes, Austin Peay State University Department of Physics and Astronomy, Oak Ridge National Laboratory, Oak Ridge TN 37831, American Superconductor Corp., Westborough MA 01581, University of North Georgia, Dahlonega GA 30597, Florida State University, Ecole Polytechnique, Space Telescope Science Institute, Fermi National Accelerator Lab, National Optical Astronomy Observatory, Austin Peay State Univerity, North Carolna State University, Florida Intl Univ, University of North Georgia, Clemson University, Clemson Univ, Vanderbilt University/ORNL, Vanderbilt University/Univ. of Kentucky, College of William and Mary, Louisiana State University, Presbyterian College, North Carolina State Univ, Department of Physics, Virginia Tech, Mathematical Institute, University of Oxford, Virginia Tech University, Hollins University, University of Tennessee Space Institute, Davidson College, University of Tennessee, American Superconductor Corporation, University of South Alabama, North Carolina State University, James Madison University, Lousiana State University, Korea Electrotechnology Research Institute, Changwon Korea

  • Brad Cox

    North Carolnia State University, Vanderbilt University, University of South Carolina, University of Virginia, Francis Marion Univ, Oak Ridge National Laboratory, Massachusetts Institute of Technology, Florida International University, Georgia College, JINR, Tsinghua University, LBNL, GANIL, Austin Peay State University, Lehigh University, University of Pardubice, Universit\'e de Rennes, Austin Peay State University Department of Physics and Astronomy, Oak Ridge National Laboratory, Oak Ridge TN 37831, American Superconductor Corp., Westborough MA 01581, University of North Georgia, Dahlonega GA 30597, Florida State University, Ecole Polytechnique, Space Telescope Science Institute, Fermi National Accelerator Lab, National Optical Astronomy Observatory, Austin Peay State Univerity, North Carolna State University, Florida Intl Univ, University of North Georgia, Clemson University, Clemson Univ, Vanderbilt University/ORNL, Vanderbilt University/Univ. of Kentucky, College of William and Mary, Louisiana State University, Presbyterian College, North Carolina State Univ, Department of Physics, Virginia Tech, Mathematical Institute, University of Oxford, Virginia Tech University, Hollins University, University of Tennessee Space Institute, Davidson College, University of Tennessee, American Superconductor Corporation, University of South Alabama, North Carolina State University, James Madison University, Lousiana State University, Korea Electrotechnology Research Institute, Changwon Korea