Cysteine repeat domains and adjacent sequences determine distinct bone morphogenetic protein modulatory activities of the drosophila sog protein

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Title
Cysteine repeat domains and adjacent sequences determine distinct bone morphogenetic protein modulatory activities of the drosophila sog protein
Author(s)
Kweon Yu; K H Kang; P Heine; U Pyati; S Srinivasan; B Biehs; D Kimelman; E Bier
Bibliographic Citation
Genetics, vol. 166, no. 3, pp. 1323-1336
Publication Year
2004
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.
ISSN
0016-6731
Publisher
Genetics Society America
DOI
http://dx.doi.org/10.1534/genetics.166.3.1323
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > 1. Journal Articles
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