PROJECT OVERVIEW
In this project we solved the structure of the thrombopoietin receptor MPL. Thrombopoietin (TPO) is a master regulator of haematopoiesis and using this structural knowledge we designed new modified TPOs to control haematopoeisis.
PROJECT DETAILS
- Research Name Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis
- Journal Cell
- Year 2023
- Link https://doi.org/10.1016/j.cell.2023.07.037
Abstract
The thrombopoietin-MPL axis plays essential roles in hematopoietic stem cell biology and platelet production. Cryo-EM structure of the dimeric thrombopoietin- MPL receptor complex enabled design of biased agonists that tune intracellular signaling, thereby uncoupling the primary opposing functions of thrombopoietin signaling, hematopoietic stem cell maintenance, and differentiation.
Authors:
Naotaka Tsutsumi,1,2,3,4,* Zahra Masoumi,5 Sophie C. James,5 Julie A. Tucker,5 Hauke Winkelmann,6 William Grey,5 Lora K. Picton,1 Lucie Moss,5 Steven C. Wilson,1,2 Nathanael A. Caveney,1,2 Kevin M. Jude,1,2,3 Cornelius Gati,2,7 Jacob Piehler,6 Ian S. Hitchcock,5,* and K. Christopher Garcia1,2,3,8,*
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA
2Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
3Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
4Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan
5York Biomedical Research Institute, Department of Biology, University of York, Heslington, York YO10 5DD, UK
6Department of Biology/Chemistry and Center of Cellular Nanoanalytics, Osnabru ̈ ck University, 49076 Osnabru ̈ ck, Germany
7Biosciences Division, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA
8Lead contact
*Correspondence: [email protected] (N.T.), [email protected] (I.S.H.), [email protected] (K.C.G.)