Nuclear magnetic resonance and circular dichroism study of metastin (Kisspeptin-54) structure in solution

Clin Exp Metastasis. 2009;26(6):527-33. doi: 10.1007/s10585-009-9252-0. Epub 2009 Mar 24.

Abstract

KISS1 was first discovered as a metastasis suppressor, but also plays crucial roles in the onset of puberty. The KISS1 gene encodes a secreted protein of 145 amino acids that exhibits no sequence similarity with any known proteins. KISS1 protein is proteolytically processed to generate a number of so-called kisspeptins (KP), the most well characterized is known as KP-54 or metastin. KP-54 is carboxy-terminally amidated and binds to and activates the KISS1 receptor (KISS1R). The current studies were undertaken in order to determine structure of KP-54 using nuclear magnetic resonance and circular dichroism. KP-54 is mostly disordered both in water and in trifluoroethanol/water mixed solvent, with no structural motifs. In sodium dodecyl sulfate micelles, KP-54 remains mostly disordered except for a small increase in helical propensity (from 3.7% in water to 9.9% in micelles). Despite this apparent lack of structure, KP-54 is biologically active. The intrinsic disorder of KP-54 may confer advantages in its ability to recognize and bind a wide range of target proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism / methods*
  • Kisspeptins
  • Magnetic Resonance Spectroscopy / methods*
  • Molecular Sequence Data
  • Solutions
  • Tumor Suppressor Proteins / chemistry*

Substances

  • KISS1 protein, human
  • Kisspeptins
  • Solutions
  • Tumor Suppressor Proteins