Brain expressed and X-linked (Bex) proteins are intrinsically disordered proteins (IDPs) and form new signaling hubs

PLoS One. 2015 Jan 22;10(1):e0117206. doi: 10.1371/journal.pone.0117206. eCollection 2015.


Intrinsically disordered proteins (IDPs) are abundant in complex organisms. Due to their promiscuous nature and their ability to adopt several conformations IDPs constitute important points of network regulation. The family of Brain Expressed and X-linked (Bex) proteins consists of 5 members in humans (Bex1-5). Recent reports have implicated Bex proteins in transcriptional regulation and signaling pathways involved in neurodegeneration, cancer, cell cycle and tumor growth. However, structural and biophysical data for this protein family is almost non-existent. We used bioinformatics analyses to show that Bex proteins contain long regions of intrinsic disorder which are conserved across all members. Moreover, we confirmed the intrinsic disorder by circular dichroism spectroscopy of Bex1 after expression and purification in E. coli. These observations strongly suggest that Bex proteins constitute a new group of IDPs. Based on these findings, together with the demonstrated promiscuity of Bex proteins and their involvement in different signaling pathways, we propose that Bex family members play important roles in the formation of protein network hubs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circular Dichroism
  • Humans
  • Mice
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction*


  • BEX1 protein, human
  • Bex1 protein, mouse
  • Nerve Tissue Proteins
  • Recombinant Proteins

Grant support

Ministry of Economy and Competitiveness (MINECO) from the Government of Spain. Projects: BFU2010-15276 and BFU2013-42746-P to MV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.