title: Structural characterization of mammalian bHLH-PAS transcription factors.
abstract: The mammalian basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) transcription factors share common architectural features that include a bHLH DNA-binding domain and tandemly positioned PAS domains. The sixteen members of this family include the hypoxia-inducible factors (HIF-1α and HIF-2α), ARNT (also known as HIF-1β), CLOCK and BMAL1. Most bHLH-PAS proteins have been genetically linked to variety of diseases in humans, including cancers, metabolic syndromes and psychiatric conditions. To function as transcription factors, the bHLH-PAS proteins must form heterodimeric complexes. Recent crystallographic studies of HIF-α-ARNT and CLOCK-BMAL1 complexes have unveiled the organization of their multi-domain bHLH-PAS-A-PAS-B segments, revealing how these architectures can give rise to unique patterns of heterodimerization. As our structural understanding becomes better integrated with ligand-discovery and target gene identification, a more comprehensive picture of their architectural and functional properties will emerge.
authors.affiliation: Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA; State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, 266237, China.
authors.forename: Dalei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA. Electronic address: frastinejad@sbpdiscovery.org.
authors.forename: Fraydoon
authors.initials: F
authors.lastname: Rastinejad
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D000072417:Protein Domains; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit