Screening and analysis of agouti signaling protein interaction partners in Pelodiscus sinensis suggests a role in lipid metabolism

Int J Biol Macromol. 2020 Aug 15:157:695-705. doi: 10.1016/j.ijbiomac.2019.11.229. Epub 2019 Nov 30.

Abstract

Agouti signaling protein (ASP) is a secreted paracrine protein that has been widely reported to function in melanogenesis and obesity and could potentially be a core protein that regulates the color and fatty phenotype of P. sinensis. In this study, we screened out interacting proteins of ASP by combined co-immunoprecipitation mass spectrometry (CoIP-MS), yeast two hybrid (Y2H) analysis, and computational predictions. We performed docking of ASP with its well-known receptor melanocortin receptor 4 (MC4R) to predict the binding capacity and to screen out actual ASP interacting proteins, CoIP-MS was performed where identified 32 proteins that could bind with ASP and Y2H confirmed seven proteins binding with ASP directly. CoIP-MS and Y2H screening results including PPI prediction revealed that vitronectin (VTN), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), and filamin B (FLNB) were the key interacting proteins of ASP. VTN, APOA1, and APOB are functional proteins in lipid metabolism and various skin disorders, suggesting ASP may function in lipid metabolism through these partners. This study provided protein-protein interaction information of ASP, and the results will promote further research into the diverse roles of ASP, as well as its binding partners, and their function in different strains of P. sinensis.

Keywords: Agouti signaling protein; Interacting proteins; Lipid metabolism; Melanogenesis; Pelodiscus sinensis.

MeSH terms

  • Agouti Signaling Protein / chemistry
  • Agouti Signaling Protein / genetics
  • Agouti Signaling Protein / metabolism*
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Gene Expression
  • Humans
  • Lipid Metabolism*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Phylogeny
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • Structure-Activity Relationship
  • Turtles / metabolism*

Substances

  • Agouti Signaling Protein
  • Carrier Proteins