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

Academic Article

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. © 2009 Springer Science+Business Media B.V.
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    Digital Object Identifier (doi)

    Author List

  • Shin R; Welch DR; Mishra VK; Nash KT; Hurst DR; Rama Krishna N
  • Start Page

  • 527
  • End Page

  • 533
  • Volume

  • 26
  • Issue

  • 6