bHLH–PAS Proteins: Their Structure and Intrinsic Disorder
Open Access
- 25 July 2019
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 20 (15), 3653
- https://doi.org/10.3390/ijms20153653
Abstract
The basic helix–loop–helix/Per-ARNT-SIM (bHLH–PAS) proteins are a class of transcriptional regulators, commonly occurring in living organisms and highly conserved among vertebrates and invertebrates. These proteins exhibit a relatively well-conserved domain structure: the bHLH domain located at the N-terminus, followed by PAS-A and PAS-B domains. In contrast, their C-terminal fragments present significant variability in their primary structure and are unique for individual proteins. C-termini were shown to be responsible for the specific modulation of protein action. In this review, we present the current state of knowledge, based on NMR and X-ray analysis, concerning the structural properties of bHLH–PAS proteins. It is worth noting that all determined structures comprise only selected domains (bHLH and/or PAS). At the same time, substantial parts of proteins, comprising their long C-termini, have not been structurally characterized to date. Interestingly, these regions appear to be intrinsically disordered (IDRs) and are still a challenge to research. We aim to emphasize the significance of IDRs for the flexibility and function of bHLH–PAS proteins. Finally, we propose modern NMR methods for the structural characterization of the IDRs of bHLH–PAS proteins.Keywords
Funding Information
- The National Science Centre (NCN): (UMO-2017/27/N/NZ1/01783, UMO-2018/28/T/NZ1/00337, a statutory activity subsidy for the Faculty of Chemistry of Wroclaw University of Science and Technology 0401/0143/18)
This publication has 95 references indexed in Scilit:
- Intermolecular recognition revealed by the complex structure of human CLOCK-BMAL1 basic helix-loop-helix domains with E-box DNACell Research, 2012
- The Drosophila Juvenile Hormone Receptor Candidates Methoprene-tolerant (MET) and Germ Cell-expressed (GCE) Utilize a Conserved LIXXL Motif to Bind the FTZ-F1 Nuclear ReceptorJournal of Biological Chemistry, 2012
- Molecular and functional analysis of Drosophila single-minded larval central brain expressionGene Expression Patterns, 2011
- Coactivator recruitment: A new role for PAS domains in transcriptional regulation by the bHLH‐PAS familyJournal of Cellular Physiology, 2010
- PONDR-FIT: A meta-predictor of intrinsically disordered amino acidsBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2010
- Biophysical characterization of intrinsically disordered proteinsCurrent Opinion in Structural Biology, 2009
- Artificial ligand binding within the HIF2α PAS-B domain of the HIF2 transcription factorProceedings of the National Academy of Sciences, 2009
- Characterization of Molecular Recognition Features, MoRFs, and Their Binding PartnersJournal of Proteome Research, 2007
- IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy contentBioinformatics, 2005
- Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation ModelingBiophysical Journal, 2000