Structural and functional characterization of soluble endoglin receptor.
Endoglin, an accessory membrane receptor of transforming growth factor-beta (TGF-beta)1, modulates the cellular response to TGF-beta via its interaction with type I and II TGF-beta receptors. It has been considered a promising target for the development of therapeutics and cancer markers. We have established stable CHO cell lines that efficiently secrete soluble endoglin (s-endoglin) fused with human growth hormone. Two oligomeric forms were observed in a homogeneous preparation of s-endoglin, as a dimer and a tetramer. The dimeric s-endoglin enhanced TGF-beta responsiveness in U937 cells, thus proving its potential for therapeutic applications. Small angle X-ray scattering (SAXS) experiments revealed elongated conformations of both dimeric and tetrameric s-endoglins in solution, suggesting that s-endoglin might undergo conformational adaptations upon TGF-beta binding. The current results provide important references and material for high-resolution structural studies and for medical applications of s-endoglin.
Van Le
Binh
B
Department of Molecular Cell Biology, Samsung Biomedical Research institute, Sungkyunkwan University School of Medicine, 300 Chunchun-Dong, Suwon 440-746, Republic of Korea.
Franke
Daniel
D
Svergun
Dmitri I
DI
Han
Taehee
T
Hwang
Hye-Yeon
HY
Kim
Kyeong Kyu
KK
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000071063:Endoglin; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D011487:Protein Conformation; D055503:Protein Multimerization; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012542:Scattering, Radiation; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D014965:X-Rays
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D016211:Transforming Growth Factor alpha; D008156:Luciferases