X-ray and NMR structure of human Bcl-x(L), an inhibitor of programmed cell death
X-ray and NMR structure of human Bcl-x(L), an inhibitor of programmed cell death
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DOI：
10.1038/381335a0
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发表时间：
1996-05-23
期刊：
影响因子：
64.8
通讯作者：
Fesik, SW
中科院分区：
文献类型：
--
作者：
Muchmore, SW;Sattler, M;Fesik, SW
Bcl-2蛋白家族通过一种未知的机制调节程序性细胞死亡（1）。在这里，我们描述了Bcl-2家族成员Bcl-x（L）的晶体和溶液结构（参考文献2）。该结构由两个中心的，主要是疏水性的α-螺旋组成，其被两亲性螺旋包围。发现连接螺旋α 1和α 2的60个残基的环是柔性的，并且对于抗凋亡活性是非必需的。三个功能上重要的Bcl-2同源区（BH 1、BH 2和BH 3）（3-5）在空间上非常接近，并形成一个细长的疏水裂缝，可能代表其他Bcl-2家族成员的结合位点。Bcl-x（L）中α-螺旋的排列使人联想到细菌毒素的膜易位结构域，特别是白喉毒素和大肠杆菌素（6）。结构相似性可能为Bcl-2蛋白家族的作用机制提供线索。
THE Bcl-2 family of proteins regulate programmed cell death by an unknown mechanism(1). Here we describe the crystal and solution structures of a Bcl-2 family member, Bcl-x(L) (ref. 2). The structures consist of two central, primarily hydrophobic alpha-helices, which are surrounded by amphipathic helices. A 60-residue loop connecting helices alpha 1 and alpha 2 was found to be flexible and non-essential for anti-apoptotic activity. The three functionally important Bcl-2 homology regions (BH1, BH2 and BH3)(3-5) are in close spatial proximity and form an elongated hydrophobic cleft that may represent the binding site for other Bcl-2 family members. The arrangement of the alpha-helices in Bcl-x(L) is reminiscent of the membrane translocation domain of bacterial toxins, in particular diphtheria toxin and the colicins(6). The structural similarity may provide a clue to the mechanism of action of the Bcl-2 family of proteins.