title: Cysteine repeat domains and adjacent sequences determine distinct bone morphogenetic protein modulatory activities of the Drosophila Sog protein.
abstract: The Drosophila short gastrulation gene (sog) encodes a large extracellular protein (Sog) that inhibits signaling by BMP-related ligands. Sog and its vertebrate counterpart Chordin contain four copies of a cysteine repeat (CR) motif defined by 10 cysteine residues spaced in a fixed pattern and a tryptophan residue situated between the first two cysteines. Here we present a structure-function analysis of the CR repeats in Sog, using a series of deletion and point mutation constructs, as well as constructs in which CR domains have been swapped. This analysis indicates that the CR domains are individually dispensable for Sog function but that they are not interchangeable. These studies reveal three different types of Sog activity: intact Sog, which inhibits signaling mediated by the ligand Glass bottom boat (Gbb), a more broadly active class of BMP antagonist referred to as Supersog, and a newly identified activity, which may promote rather than inhibit BMP signaling. Analysis of the activities of CR swap constructs indicates that the CR domains are required for full activity of the various forms of Sog but that the type of Sog activity is determined primarily by surrounding protein sequences. Cumulatively, our analysis suggests that CR domains interact physically with adjacent protein sequences to create forms of Sog with distinct BMP modulatory activities.
authors.affiliation: Section of Cell and Developmental Biology and Center for Molecular Genetics, University of California, San Diego, California 92093-0349, USA.
authors.forename: Kweon
authors.initials: K
authors.lastname: Yu
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Kang
authors.forename: Petra
authors.initials: P
authors.lastname: Heine
authors.forename: Ujwal
authors.initials: U
authors.lastname: Pyati
authors.forename: Shaila
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Brian
authors.initials: B
authors.lastname: Biehs
authors.forename: David
authors.initials: D
authors.lastname: Kimelman
authors.forename: Ethan
authors.initials: E
authors.lastname: Bier
mesh_terms: D000409:Alanine / Q000378:metabolism; D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry*; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008024:Ligands; D008845:Microinjections; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry; D014921:Wings, Animal / Q000254:growth & development; D014981:Xenopus / Q000196:embryology
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D008024:Ligands; C091428:sog protein, Drosophila; D012313:RNA; D014364:Tryptophan; D003545:Cysteine; D000409:Alanine