(封面图片:gp130/LIF-R/CNTF-Rα/CNTF四元复合物的非对称构造,图中分别显示了白血病抑制因子受体LIF-R(紫色)、gp130(蓝色)、睫状神经营养因子CNTF(黄色)、以及CNTF受体CNTF-R(绿色)。)
白血病抑制因子受体(Leukemia Inhibitory Factor Receptor LIF-R)以及gp130是一种得到各种细胞因子广泛共享的信号受体,这些细胞因子与细胞生长、细胞分化等过程息息相关,其中就包括睫状神经营养因子(Ciliary Neurotrophic Factor CNTF)及其受体。
糖蛋白gp130是一种至少被9种细胞因子所共用的受体,并且gp130能作为白血病抑制因子受体同型或异型二聚体起到信号作用。在2008年9月5日出版的《分子细胞》(Molecular Cell)上,来自美国的一组科学家以封面文章的形式发表了他们的最新研究结果,在文章中研究人员表示,他们在生物物理和结构上确定了一种四元细胞因子受体复合体的全长、跨膜形式结构,这种细胞因子受体复合体包含gp130、LIF-R、细胞因子睫状神经营养因子及其α受体(CNTF-Rα)。
热力学分析结果显示,与合作方式形成的对称gp130/interleukin-6/IL-6Rα六聚体复合物不同的是,CNTF/ CNTF-Rα通过一种非合作的形式与gp130以及LIF-R结合,并最终形成一种非对称的1:1:1:1比例的复合物。对于全长gp130/LIF-R/CNTF-Rα/CNTF四元复合物的单粒子电子显微镜的分析证实了这种非对称的构造,其中胞外和跨膜的受体部分结合成一个连续的结构。这种细胞表面信号复合体的不对称胞外结构通过一组组织规则形成,而这种规则适用于整个细胞因子受体家族。
对于全长四元复合体而言,其结构中含有跨膜和胞内部分,LIF-R和gp130受体在近膜区结合成进入细胞膜的受体,而相关的结构分析则显示,受体的胞外和跨膜部分处之间的连接是非常强的。这种强度能使细胞外的结构震动更容易的通过细胞膜传达到细胞内。此外,文章中还例举了其它gp130家族细胞因子受体的组织规则,其中包括LIF、IL-27、IL-12等等。(生物谷Bioon.com)
生物谷推荐原始出处:
Molecular Cell,Vol 31, 737-748, 05 September 2008,Georgios Skiniotis, K. Christopher Garcia
Structural Organization of a Full-Length gp130/LIF-R Cytokine Receptor Transmembrane Complex
Georgios Skiniotis,1,6 Patrick J. Lupardus,3,4,6 Monika Martick,3,4 Thomas Walz,1,2 and K. Christopher Garcia3,4,5
1 Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
2 Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
3 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA
4 Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
5 Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
gp130 is a shared receptor for at least nine cytokines and can signal either as a homodimer or as a heterodimer with Leukemia Inhibitory Factor Receptor (LIF-R). Here, we biophysically and structurally characterize the full-length, transmembrane form of a quaternary cytokine receptor complex consisting of gp130, LIF-R, the cytokine Ciliary Neurotrophic Factor (CNTF), and its alpha receptor (CNTF-Rα). Thermodynamic analysis indicates that, unlike the cooperative assembly of the symmetric gp130/Interleukin-6/IL-6Rα hexameric complex, CNTF/CNTF-Rα heterodimerizes gp130 and LIF-R via noncooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic analysis of the full-length gp130/LIF-R/CNTF-Rα/CNTF quaternary complex elucidates an asymmetric structural arrangement, in which the receptor extracellular and transmembrane segments join as a continuous, rigid unit, poised to sensitively transduce ligand engagement to the membrane-proximal intracellular signaling regions. These studies also enumerate the organizing principles for assembly of the “tall” class of gp130 family cytokine receptor complexes including LIF, IL-27, IL-12, and others.