Mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the process.
Mechanism of diphtheria toxin catalytic domain delivery to the eukaryotic cell cytosol and the cellular factors that directly participate in the process.
复制标题
DOI：
10.3390/toxins3030294
复制
发表时间：
2011-03
期刊：
影响因子：
4.2
通讯作者：
Murphy JR
中科院分区：
文献类型：
--
作者：
Murphy JR
在过去的三十年里，对白喉和炭疽毒素的研究最终导致了对其结构功能关系的详细了解（例如，催化（C）、跨膜（T）和受体结合（R）结构域），以及鉴定它们的真核细胞表面受体，理解导致受体介导的毒素内化到内体区室中的分子事件，以及囊泡膜中孔形成所需的pH触发的构象变化。最近，一个主要的研究工作一直集中在发展的详细了解这些毒素和真核细胞因子，发挥了重要作用，在有效的易位各自的催化结构域通过trans-endosomal囊泡膜孔和交付到细胞胞质溶胶的分子之间的相互作用。在这篇综述中，我将集中在最近的研究结果，导致了更详细的了解白喉毒素催化结构域的机制被交付到真核细胞胞质溶胶。虽然还有很多工作要做，但越来越清楚的是，进入过程是通过与许多细胞因子以有序的顺序方式进行特定的相互作用来促进的。此外，由于白喉，炭疽致死因子和炭疽水肿因子都携带多个coatomer I复合物结合基序和COPI复合物已被证明在进入过程中发挥重要作用，这是可能的，在催化域进入这些不同的毒素遵循一个共同的机制的初始步骤。
Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition, since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism.
登录
查看更多内容
DOI：
10.1093/protein/11.9.811
发表时间：
1998-09-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Hu, HY;Huynh, PD;vanderSpek, JC
通讯作者：
vanderSpek, JC
DOI：
10.1073/pnas.80.22.6853
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GREENFIELD, L;BJORN, MJ;KAPLAN, DA
通讯作者：
KAPLAN, DA
影响因子：
3.3
作者：
Hudson, RT;Draper, RK
通讯作者：
Draper, RK
影响因子：
3.5
作者：
DELEERS, M;BEUGNIER, N;RUYSSCHAERT, JM
通讯作者：
RUYSSCHAERT, JM
影响因子：
56.9
作者：
KACZOREK, M;DELPEYROUX, F;TIOLLAIS, P
通讯作者：
TIOLLAIS, P