|Title||Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Lee, C., L. Kalmar, B. Xue, P. Tompa, G. W. Daughdrill, V. N. Uversky, and K-H. Han|
|Journal||Biochim Biophys Acta|
|Date Published||2014 Mar|
|Type of Article||idp|
|Keywords||Amino Acid Sequence, Dopamine and cAMP-Regulated Phosphoprotein 32, Intrinsically Disordered Proteins, Molecular Dynamics Simulation, Molecular Sequence Data, Proline, Protein Structure, Secondary, Securin, Tumor Suppressor Protein p53|
BACKGROUND: IDPs function without relying on three-dimensional structures. No clear rationale for such a behavior is available yet. PreSMos are transient secondary structures observed in the target-free IDPs and serve as the target-binding "active" motifs in IDPs. Prolines are frequently found in the flanking regions of PreSMos. Contribution of prolines to the conformational stability of the helical PreSMos in IDPs is investigated.METHODS: MD simulations are performed for several IDP segments containing a helical PreSMo and the flanking prolines. To measure the influence of flanking-prolines on the structural content of a helical PreSMo calculations were done for wild type as well as for mutant segments with Pro→Asp, His, Lys, or Ala. The change in the helicity due to removal of a proline was measured both for the PreSMo region and for the flanking regions.RESULTS: The α-helical content in ~70% of the helical PreSMos at the early stage of simulation decreases due to replacement of an N-terminal flanking proline by other residues whereas the helix content in nearly all PreSMos increases when the same replacements occur at the C-terminal flanking region. The helix destabilizing/terminating role of the C-terminal flanking prolines is more pronounced than the helix promoting effect of the N-terminal flanking prolines.GENERAL SIGNIFICANCE: This work represents a novel example demonstrating that a proline is encoded in an IDP with a defined purpose. The helical PreSMos presage their target-bound conformations. As they most likely mediate IDP-target binding via conformational selection their helical content can be an important feature for IDP function.
|Alternate Journal||Biochim. Biophys. Acta|
Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins.