Li Qingxin, Wong Ying Lei, Yueqi Lee Michelle, Li Yan, Kang CongBao
Institute of Chemical &Engineering Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), Singapore, 138669 Singapore.
Sci Rep. 2015 Aug 28;5:13586. doi: 10.1038/srep13586.
Erythropoiesis is regulated by the erythropoietin receptor (EpoR) binding to its ligand. The transmembrane domain (TMD) and the juxtamembrane (JM) regions of the EpoR are important for signal transduction across the cell membrane. We report a solution NMR study of the mouse erythropoietin receptor (mEpoR) comprising the TMD and the JM regions reconstituted in dodecylphosphocholine (DPC) micelles. The TMD and the C-terminal JM region of the mEpoR are mainly α-helical, adopting a similar structure to those of the human EpoR. Residues from S216 to T219 in mEpoR form a short helix. Relaxation study demonstrates that the TMD of the mEpoR is rigid whilst the N-terminal region preceding the TMD is flexible. Fluorescence spectroscopy and sequence analysis indicate that the C-terminal JM region is exposed to the solvent. Helix wheel result shows that there is hydrophilic patch in the TMD of the mEpoR formed by residues S231, S238 and T242, and these residues might be important for the receptor dimerization.
红细胞生成受促红细胞生成素受体(EpoR)与其配体结合的调控。EpoR的跨膜结构域(TMD)和近膜(JM)区域对于跨细胞膜的信号转导很重要。我们报道了一项针对小鼠促红细胞生成素受体(mEpoR)的溶液核磁共振研究,该受体由在十二烷基磷酸胆碱(DPC)胶束中重构的TMD和JM区域组成。mEpoR的TMD和C端JM区域主要呈α螺旋结构,与人EpoR的结构相似。mEpoR中从S216到T219的残基形成一个短螺旋。弛豫研究表明,mEpoR的TMD是刚性的,而TMD之前的N端区域是柔性的。荧光光谱和序列分析表明,C端JM区域暴露于溶剂中。螺旋轮结果显示,mEpoR的TMD中由残基S231、S238和T242形成一个亲水区,这些残基可能对受体二聚化很重要。