| First Author | Mancour LV | Year | 2012 |
| Journal | Mol Cell | Volume | 48 |
| Issue | 4 | Pages | 655-61 |
| PubMed ID | 23063524 | Mgi Jnum | J:192957 |
| Mgi Id | MGI:5467159 | Doi | 10.1016/j.molcel.2012.09.003 |
| Citation | Mancour LV, et al. (2012) Ligand-induced architecture of the leptin receptor signaling complex. Mol Cell 48(4):655-61 |
| abstractText | Despite the crucial impact of leptin signaling on metabolism and body weight, little is known about the structure of the liganded leptin receptor (LEP-R) complex. Here, we applied single-particle electron microscopy (EM) to characterize the architecture of the extracellular region of LEP-R alone and in complex with leptin. We show that unliganded LEP-R displays significant flexibility in a hinge region within the cytokine homology region 2 (CHR2) that is connected to rigid membrane-proximal FnIII domains. Leptin binds to CHR2 in order to restrict the flexible hinge and the disposition of the FnIII "legs." Through a separate interaction, leptin engages the Ig-like domain of a second liganded LEP-R, resulting in the formation of a quaternary signaling complex. We propose that the membrane proximal domain rigidification in the context of a liganded cytokine receptor dimer is a key mechanism for the transactivation of Janus kinases (Jaks) bound at the intracellular receptor region. |
