IDDomainSpotter: Compositional bias reveals domains in long disordered protein regions—Insights from transcription factors

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Protein domains constitute regions of distinct structural properties and molecular functions that are retained when removed from the rest of the protein. However, due to the lack of tertiary structure, the identification of domains has been largely neglected for long (>50 residues) intrinsically disordered regions. Here we present a sequence-based approach to assess and visualize domain organization in long intrinsically disordered regions based on compositional sequence biases. An online tool to find putative intrinsically disordered domains (IDDomainSpotter) in any protein sequence or sequence alignment using any particular sequence trait is available at https://www.bio.ku.dk/sbinlab/IDDomainSpotter. Using this tool, we have identified a putative domain enriched in hydrophilic and disorder-promoting residues (Pro, Ser, and Thr) and depleted in positive charges (Arg and Lys) bordering the folded DNA-binding domains of several transcription factors (p53, GCR, NAC46, MYB28, and MYB29). This domain, from two different MYB transcription factors, was characterized biophysically to determine its properties. Our analyses show the domain to be extended, dynamic and highly disordered. It connects the DNA-binding domain to other disordered domains and is present and conserved in several transcription factors from different families and domains of life. This example illustrates the potential of IDDomainSpotter to predict, from sequence alone, putative domains of functional interest in otherwise uncharacterized disordered proteins.

Original languageEnglish
JournalProtein Science
Volume29
Issue number1
Pages (from-to)169-183
Number of pages15
ISSN0961-8368
DOIs
Publication statusPublished - 2020

Bibliographical note

Special Issue: Tools for Protein Science

    Research areas

  • compositional bias, DNA-binding domain, domain, IDDomainSpotter, IDPs, low-complexity regions, NMR, p53, plant MYB protein, transactivation domain, transcription factor

ID: 234448370