title: Nuclear magnetic resonance and circular dichroism study of metastin (Kisspeptin-54) structure in solution.
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.
authors.affiliation: Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Shin
authors.forename: Danny R
authors.initials: DR
authors.lastname: Welch
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Mishra
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Nash
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Hurst
authors.forename: N
authors.initials: N
authors.lastname: Rama Krishna
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism / Q000379:methods*; D059648:Kisspeptins; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008969:Molecular Sequence Data; D012996:Solutions; D025521:Tumor Suppressor Proteins / Q000737:chemistry*
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D012996:Solutions; D025521:Tumor Suppressor Proteins