Qian Shuo, Wang Wangchen, Yang Lin, Huang Huey W
Department of Physics and Astronomy, Rice University, Houston, TX 77251, USA.
Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17379-83. doi: 10.1073/pnas.0807764105. Epub 2008 Nov 5.
The structures of transmembrane pores formed by a large family of pore-forming proteins and peptides are unknown. These proteins, whose secondary structures are predominantly alpha-helical segments, and many peptides form pores in membranes without a crystallizable protein assembly, contrary to the family of beta-pore-forming proteins, which form crystallizable beta-barrel pores. Nevertheless, a protein-induced pore in membranes is commonly assumed to be a protein channel. Here, we show a type of peptide-induced pore that is not framed by a peptide structure. Peptide-induced pores in multiple bilayers were long-range correlated into a periodically ordered lattice and analyzed by X-ray diffraction. We found the pores induced by Bax-derived helical peptides were at least partially framed by a lipid monolayer. Evidence suggests that the formation of such lipidic pores is a major mechanism for alpha-pore-forming proteins, including apoptosis-regulator Bax.
一大类成孔蛋白和肽所形成的跨膜孔结构尚不清楚。这些蛋白质的二级结构主要是α螺旋片段，并且许多肽在膜中形成孔，却没有可结晶的蛋白质组装体，这与形成可结晶β桶状孔的β成孔蛋白家族不同。然而，膜中由蛋白质诱导形成的孔通常被认为是蛋白质通道。在此，我们展示了一种不由肽结构构成框架的肽诱导孔。多个双层膜中的肽诱导孔呈长程关联，形成周期性有序晶格，并通过X射线衍射进行分析。我们发现由Bax衍生的螺旋肽诱导形成的孔至少部分地由脂质单层构成框架。有证据表明，这种脂质孔的形成是包括凋亡调节因子Bax在内的α成孔蛋白的主要机制。
