PUBLICATION
Structural Adaptation in Its Orphan Domain Engenders Betaglycan with an Alternate Mode of Growth Factor Binding Relative to Endoglin
- Authors
- Kim, S.K., Whitley, M.J., Krzysiak, T.C., Hinck, C.S., Taylor, A.B., Zwieb, C., Byeon, C.H., Zhou, X., Mendoza, V., López-Casillas, F., Furey, W., Hinck, A.P.
- ID
- ZDB-PUB-200513-10
- Date
- 2019
- Source
- Structure (London, England : 1993) 27: 1427-1442.e4 (Journal)
- Registered Authors
- Keywords
- SAXS, SPR, X-ray crystallography, betaglycan, cardiac development, cell signaling, cell surface receptor, co-receptor, endoglin, transforming growth factor beta (TGF-β)
- MeSH Terms
-
- Animals
- Bone Morphogenetic Proteins/metabolism
- Endoglin/chemistry*
- Endoglin/metabolism*
- Growth Differentiation Factor 2/metabolism
- HEK293 Cells
- Humans
- Protein Structure, Secondary
- Proteoglycans/metabolism*
- Rats
- Receptors, Transforming Growth Factor beta/metabolism*
- Scattering, Small Angle
- Transforming Growth Factor beta/metabolism*
- X-Ray Diffraction
- Zebrafish
- PubMed
- 31327662 Full text @ Structure
Citation
Kim, S.K., Whitley, M.J., Krzysiak, T.C., Hinck, C.S., Taylor, A.B., Zwieb, C., Byeon, C.H., Zhou, X., Mendoza, V., López-Casillas, F., Furey, W., Hinck, A.P. (2019) Structural Adaptation in Its Orphan Domain Engenders Betaglycan with an Alternate Mode of Growth Factor Binding Relative to Endoglin. Structure (London, England : 1993). 27:1427-1442.e4.
Abstract
Betaglycan (BG) and endoglin (ENG), homologous co-receptors of the TGF-β family, potentiate the signaling activity of TGF-β2 and inhibin A, and BMP-9 and BMP-10, respectively. BG exists as monomer and forms 1:1 growth factor (GF) complexes, while ENG exists as a dimer and forms 2:1 GF complexes. Herein, the structure of the BG orphan domain (BGO) reveals an insertion that blocks the region that the endoglin orphan domain (ENGO) uses to bind BMP-9, preventing it from binding in the same manner. Using binding studies with domain-deleted forms of TGF-β and BGO, as well as small-angle X-ray scattering data, BGO is shown to bind its cognate GF in an entirely different manner compared with ENGO. The alternative interfaces likely engender BG and ENG with the ability to selectively bind and target their cognate GFs in a unique temporal-spatial manner, without interfering with one another or other TGF-β family GFs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping