对红细胞生成素受体在胶束中的跨膜结构域和近膜区域的结构洞察。
Structural insight into the transmembrane domain and the juxtamembrane region of the erythropoietin receptor in micelles.
作者信息
Li Qingxin, Wong Ying Lei, Huang Qiwei, Kang CongBao
机构信息
Institute of Chemical & Engineering Sciences, Technology and Research (A(?)STAR), Singapore.
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A(?)STAR), Singapore.
出版信息
Biophys J. 2014 Nov 18;107(10):2325-36. doi: 10.1016/j.bpj.2014.10.013.
Erythropoietin receptor (EpoR) dimerization is an important step in erythrocyte formation. Its transmembrane domain (TMD) and juxtamembrane (JM) region are essential for signal transduction across the membrane. A construct compassing residues S212-P259 and containing the TMD and JM region of the human EpoR was purified and reconstituted in detergent micelles. The solution structure of the construct was determined in dodecylphosphocholine (DPC) micelles by solution NMR spectroscopy. Structural and dynamic studies demonstrated that the TMD and JM region are an ?-helix in DPC micelles, whereas residues S212-D224 at the N-terminus of the construct are not structured. The JM region is a helix that contains a hydrophobic patch formed by conserved hydrophobic residues (L253, I257, and W258). Nuclear Overhauser effect analysis, fluorescence spectroscopy, and paramagnetic relaxation enhancement experiments suggested that the JM region is exposed to the solvent. The structures of the TMD and JM region of the mouse EpoR were similar to those of the human EpoR.
促红细胞生成素受体（EpoR）二聚化是红细胞形成过程中的重要一步。其跨膜结构域（TMD）和近膜（JM）区域对于跨膜信号转导至关重要。一种包含人EpoR的TMD和JM区域、涵盖残基S212 - P259的构建体被纯化并在去污剂胶束中重构。通过溶液核磁共振光谱法在十二烷基磷酸胆碱（DPC）胶束中确定了该构建体的溶液结构。结构和动力学研究表明，在DPC胶束中TMD和JM区域呈α螺旋，而构建体N端的残基S212 - D224没有形成特定结构。JM区域是一个螺旋，包含由保守疏水残基（L253、I257和W258）形成的疏水斑块。核Overhauser效应分析、荧光光谱和顺磁弛豫增强实验表明JM区域暴露于溶剂中。小鼠EpoR的TMD和JM区域结构与人EpoR的相似。
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