Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
105
70-POS
Board 30
Conformational Effects of Threonine Phosphorylation in Proline-rich Disordered Motifs
Gabriel A. Lucero
1
,
Paul S. Nerenberg
2,3
.
2
California State University, Los Angeles, Los Angeles, CA, USA,
3
California State University,
Los Angeles, Los Angeles, CA, USA.
1
California State University, Los Angeles, Los Angeles,
CA, USA,
The experimental literature regarding the conformational effects of threonine (Thr)
phosphorylation in intrinsically disordered proteins/regions presents an apparent paradox. In
some contexts, Thr phosphorylation appears to stabilize beta conformations, while in others –
including a proline-rich region of the tau protein – it appears to stabilize PPII conformations. In
this work we present MD simulations of several small peptide systems that suggest that the
identity of the residue immediately C-terminal to the Thr phosphorylation site is the primary
determinant of how the conformational ensembles of these peptides change upon
phosphorylation. These data help resolve the aforementioned paradox by demonstrating that the
existence of a proline residue in this position prevents the formation of a phosphate-to-backbone
hydrogen bond that would otherwise stabilize beta conformations. This in turn has implications
for the role of phosphorylation in proline-rich motifs, which are both often disordered and
recognition sites for protein-protein interactions. Finally, our simulations provide specific,
testable hypotheses that can be confirmed – or falsified – with appropriate NMR experiments.