| Autor: |
Lantz C; Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States., Xi Z; Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States., Rider RL; Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States., Walker TE; Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States., Hebert M; Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States., Russell DH; Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States. |
| Abstrakt: |
Interactions of the peptide substance P (SP) (RPKPQQFFGLM-NH 2 ) with trimethylamine N -oxide (TMAO) were investigated by using cryo-ion mobility-mass spectrometry (cryo-IM-MS), variable-temperature (278-358 K) electrospray ionization (vT-ESI) MS, and molecular dynamics (MD) simulations. Cryo-IM-MS provides evidence that cold solutions containing SP and TMAO yield abundant hydrated SP dimer ions, but dimer formation is inhibited in solutions that also contain urea. In addition, we show that SP dimer formation at cold solution temperatures (<298 K) is favored when TMAO interacts with the hydrophobic C-terminus of SP and is subject to reduced entropic penalty when compared to warmer solution conditions (>298 K). MD simulations show that TMAO lowers the free energy barrier for dimerization and that monomers dimerize by forming hydrogen bonds (HBs). Moreover, differences in oligomer abundances for SP mutants (P4A, P2,4A, G9P, and P2,4A/G9P) provide evidence that oligomerization facilitated by TMAO is sensitive to the cis / trans orientation of residues at positions 2, 4, and 9. |
