Tweten Rodney K, Hotze Eileen M, Wade Kristin R
Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; email:
Annu Rev Microbiol. 2015;69:323-40. doi: 10.1146/annurev-micro-091014-104233.
The mechanism by which the cholesterol-dependent cytolysins (CDCs) assemble their giant β-barrel pore in cholesterol-rich membranes has been the subject of intense study in the past two decades. A combination of structural, biophysical, and biochemical analyses has revealed deep insights into the series of complex and highly choreographed secondary and tertiary structural transitions that the CDCs undergo to assemble their β-barrel pore in eukaryotic membranes. Our knowledge of the molecular details of these dramatic structural changes in CDCs has transformed our understanding of how giant pore complexes are assembled and has been critical to our understanding of the mechanisms of other important classes of pore-forming toxins and proteins across the kingdoms of life. Finally, there are tantalizing hints that the CDC pore-forming mechanism is more sophisticated than previously imagined and that some CDCs are employed in pore-independent processes.
在过去二十年中，胆固醇依赖性细胞溶素（CDCs）在富含胆固醇的膜中组装其巨大β-桶状孔的机制一直是深入研究的主题。结构、生物物理和生化分析相结合，揭示了CDCs在真核细胞膜中组装其β-桶状孔所经历的一系列复杂且高度协调的二级和三级结构转变的深刻见解。我们对CDCs中这些显著结构变化的分子细节的了解，改变了我们对巨大孔复合物如何组装的理解，并且对于我们理解生命各王国中其他重要类别的成孔毒素和蛋白质的机制至关重要。最后，有诱人的线索表明，CDC的成孔机制比以前想象的更为复杂，并且一些CDCs被用于非孔依赖过程。
