The metastasis suppressor KISS1 is an intrinsically disordered protein slightly more extended than a random coil

PLoS One. 2017 Feb 16;12(2):e0172507. doi: 10.1371/journal.pone.0172507. eCollection 2017.

Abstract

The metastasis suppressor KISS1 is reported to be involved in the progression of several solid neoplasias, making it a promising molecular target for controlling their metastasis. The KISS1 sequence contains an N-terminal secretion signal and several dibasic sequences that are proposed to be the proteolytic cleavage sites. We present the first structural characterization of KISS1 by circular dichroism, multi-angle light scattering, small angle X-Ray scattering and NMR spectroscopy. An analysis of the KISS1 backbone NMR chemical shifts does not reveal any preferential conformation and deviation from a random coil ensemble. The backbone 15N transverse relaxation times indicate a mildly reduced mobility for two regions that are rich in bulky residues. The small angle X-ray scattering curve of KISS1 is likewise consistent with a predominantly random coil ensemble, although an ensemble optimization analysis indicates some preference for more extended conformations possibly due to positive charge repulsion between the abundant basic residues. Our results support the hypothesis that KISS1 mostly samples a random coil conformational space, which is consistent with its high susceptibility to proteolysis and the generation of Kisspeptin fragments.

MeSH terms

  • Circular Dichroism
  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Kisspeptins / chemistry*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation*
  • Protein Folding
  • Scattering, Small Angle

Substances

  • Intrinsically Disordered Proteins
  • KISS1 protein, human
  • Kisspeptins

Grant support

Support was provided by: Ministerio de Economía y Competitividad [http://www.mineco.gob.es/portal/site/mineco/] CTQ2014-56966-R to FJB; Agence National de Recherche [http://www.agence-nationale-recherche.fr/] SPIN-HD – ANR Chaires d’Excellence to PB; ATIP-Avenir [http://www.aviesan.fr/en/aviesan/home/atip-avenir-program] to PB; The French Infrastructure for Integrated Structural Biology (FRISBI – ANR-10-INSB-05-01) to PB.