| First Author | Greenwald J | Year | 2004 |
| Journal | Mol Cell | Volume | 15 |
| Issue | 3 | Pages | 485-9 |
| PubMed ID | 15304227 | Mgi Jnum | J:91816 |
| Mgi Id | MGI:3050899 | Doi | 10.1016/j.molcel.2004.07.011 |
| Citation | Greenwald J, et al. (2004) A flexible activin explains the membrane-dependent cooperative assembly of TGF-beta family receptors. Mol Cell 15(3):485-9 |
| abstractText | A new crystal structure of activin in complex with the extracellular domain of its type II receptor (ActRIIb-ECD) shows that the ligand exhibits an unexpected flexibility. The motion in the activin dimer disrupts its type I receptor interface, which may account for the disparity in its affinity for type I versus type II receptors. We have measured the affinities of activin and its antagonist inhibin for ActRIIb-ECD and found that the affinity of the 2-fold symmetric homodimer activin for ActRIIb-ECD depends on the availability of two spatially coupled ActRIIb-ECD molecules, whereas the affinity of the heterodimer inhibin does not. Our results indicate that activin's affinity for its two receptor types is greatly influenced by their membrane-restricted setting. We propose that activin affinity is modulated by the ligand flexibility and that cooperativity is achieved by binding to two ActRII chains that immobilize activin in a type I binding-competent orientation. |
