Institute of Physical Biology, Heinrich-Heine-Universität, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Structure. 2012 Oct 10;20(10):1778-87. doi: 10.1016/j.str.2012.08.005. Epub 2012 Sep 6.
Type 1 secretion systems (T1SS) catalyze the one step protein transport across the membranes of Gram-negative bacteria and are composed of an outer membrane protein, a membrane fusion protein and an ABC transporter. The ABC transporter consists of the canonical nucleotide binding and transmembrane domains. For the toxin hemolysin A (HlyA), the ABC transporter HlyB carries an additional, N-terminal domain sharing about 40% homology to C39 peptidases, but this "C39-like domain" (CLD) is suggested to feature another, yet unknown function. Our functional and structural analysis demonstrates that the CLD is essential for secretion and that it specifically interacts with the unfolded state of HlyA. We determined the nuclear magnetic resonance structure of the CLD as well as the substrate-binding region within the CLD. This mode of action, represents a mechanism within T1SS and answers the question, how a large and unfolded substrate is protected inside the cells during secretion.
I 型分泌系统（T1SS）催化一步跨膜蛋白转运，在革兰氏阴性菌中发挥作用，由外膜蛋白、膜融合蛋白和 ABC 转运体组成。ABC 转运体由经典的核苷酸结合和跨膜结构域组成。对于毒素溶血素 A（HlyA），ABC 转运体 HlyB 携带一个额外的、N 端结构域，与 C39 肽酶约有 40%的同源性，但这个“C39 样结构域”（CLD）被认为具有另一个未知的功能。我们的功能和结构分析表明，CLD 对分泌是必需的，并且它与 HlyA 的未折叠状态特异性相互作用。我们确定了 CLD 的核磁共振结构以及 CLD 内的底物结合区域。这种作用模式代表了 T1SS 内的一种机制，并回答了一个问题，即在分泌过程中，如何在细胞内保护大而未折叠的底物。
