Characterization of the different oligomeric states of the DAN family antagonists SOSTDC1 and SOST
| Autor: | Chandramohan Kattamuri, Magdalena Czepnik, Thomas B. Thompson, Gregory Royce Gipson |
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| Rok vydání: | 2020 |
| Předmět: |
Dimer
Biophysics GDF5 Bone morphogenetic protein Biochemistry Cell Line oligomerization Avian Proteins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biochemical Techniques & Resources Structural Biology Neuroblastoma medicine Animals Humans BMP Molecular Biology Gene Research Articles Adaptor Proteins Signal Transducing 030304 developmental biology 0303 health sciences Antagonist Cell Biology medicine.disease Signaling In vitro Cell biology SOSTDC1 chemistry Bone Morphogenetic Proteins Sclerostin Protein Multimerization Chickens SOST 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bcj20200552 |
| Popis: | The DAN (differential screening-selected gene aberrative in neuroblastoma) family are a group of secreted extracellular proteins which typically bind to and antagonize BMP (bone morphogenetic protein) ligands. Previous studies have revealed discrepancies between the oligomerization state of certain DAN family members, with SOST (a poor antagonist of BMP signaling) forming a monomer while Grem1, Grem2, and NBL1 (more potent BMP antagonists) form non-disulfide linked dimers. The protein SOSTDC1 (Sclerostin domain containing protein 1) is sequentially similar to SOST, but has been shown to be a better BMP inhibitor. In order to determine the oligomerization state of SOSTDC1 and determine what effect dimerization might have on the mechanism of DAN family antagonism of BMP signaling, we isolated the SOSTDC1 protein and, using a battery of biophysical, biochemical, and structural techniques, showed that SOSTDC1 forms a highly stable non-covalent dimer. Additionally, this SOSTDC1 dimer was shown, using an in vitro cell based assay system, to be an inhibitor of multiple BMP signaling growth factors, including GDF5, while monomeric SOST was a very poor antagonist. These results demonstrate that SOSTDC1 is distinct from paralogue SOST in terms of both oligomerization and strength of BMP inhibition. |
| Databáze: | OpenAIRE |
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