title: New insights into the Orange domain of E(spl)-M8, and the roles of the C-terminal domain in autoinhibition and Groucho recruitment.
abstract: CK2 is a Ser/Thr protein kinase that regulates the activity of the Drosophila basic-helix-loop-helix (bHLH) repressor M8 encoded by the Enhancer of split Complex (E(spl)C) during neurogenesis. Specifically, phosphorylation appears to elicit a conformational change in an autoinhibited state of M8 to one that is permissive for repression. We describe biochemical and molecular modeling studies that provide new insights into repression by M8. Our studies implicate the phosphorylation domain in autoinhibition, and indicate that binding of the co-repressor Groucho (Gro) is context-dependent. Molecular modeling indicates that the Orange domain, proposed to be a specificity-determinant, may instead play a structural role, and that a conformational rearrangement of this domain may be necessary for repression. This model also provides a structural mechanism for the behavior of mutant alleles of the m8 gene. The insights gained from these studies should be applicable to the conserved metazoan bHLH repressors of the Hairy and Enhancer of Split (HES) family that are related to Drosophila M8.
authors.affiliation: Department of Biology, West Virginia University, Life Sciences Building, Morgantown, WV 26506-6057, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Eastwood
authors.forename: Chong
authors.initials: C
authors.lastname: Yin
authors.forename: Mohna
authors.initials: M
authors.lastname: Bandyopadhyay
authors.forename: Ashok
authors.initials: A
authors.lastname: Bidwai
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism; D016384:Consensus Sequence; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism*; D005123:Eye / Q000378:metabolism / Q000473:pathology; D005998:Glycine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D047390:Casein Kinase II; D029721:Drosophila Proteins; D005998:Glycine; D012097:Repressor Proteins; C492706:E(spl)m8-HLH protein, Drosophila; C091023:gro protein, Drosophila