CisTrans Isomerization of Pro(7) in Oxytocin Regulates Zn(2+) Binding. Academic Article uri icon

abstract

  • Ion mobility/mass spectrometry techniques are employed to investigate the binding of Zn(2+) to the nine-residue peptide hormone oxytocin (OT, Cys(1)-Tyr(2)-Ile(3)-Gln(4)-Asn(5)-Cys(6)-Pro(7)-Leu(8)-Gly(9)-NH2, having a disulfide bond between Cys(1) and Cys(6) residues). Zn(2+) binding to OT is known to increase the affinity of OT for its receptor [Pearlmutter, A. F., Soloff, M. S.: Characterization of the metal ion requirement for oxytocin-receptor interaction in rat mammary gland membranes. J. Biol. Chem. 254, 3899-3906 (1979)]. In the absence of Zn(2+), we find evidence for two primary OT conformations, which arise because the Cys(6)-Pro(7) peptide bond exists in both the trans- and cis-configurations. Upon addition of Zn(2+), we determine binding constants in water of KA = 1.43 0.24 and 0.42 0.12 M(-1), for the trans- and cis-configured populations, respectively. The Zn(2+) bound form of OT, having a cross section of = 235 (2), has Pro(7) in the trans-configuration, which agrees with a prior report [Wyttenbach, T., Liu, D., Bowers, M. T.: Interactions of the hormone oxytocin with divalent metal ions. J. Am. Chem. Soc. 130, 5993-6000 (2008)], in which it was proposed that Zn(2+) binds to the peptide ring and is further coordinated by interaction of the C-terminal, Pro(7)-Leu(8)-Gly(9)-NH2, tail. The present work shows that the cis-configuration of OT isomerizes to the trans-configuration upon binding Zn(2+). In this way, the proline residue regulates Zn(2+) binding to OT and, hence, is important in receptor binding. Graphical Abstract .

published proceedings

  • J Am Soc Mass Spectrom

altmetric score

  • 0.25

author list (cited authors)

  • Fuller, D. R., Glover, M. S., Pierson, N. A., Kim, D., Russell, D. H., & Clemmer, D. E.

citation count

  • 9

complete list of authors

  • Fuller, Daniel R||Glover, Matthew S||Pierson, Nicholas A||Kim, DoYong||Russell, David H||Clemmer, David E

publication date

  • August 2016