PDF(Pubmed)
Abstract：
Peptidoglycan (PG) sacculi surround the cytoplasmic membrane, maintaining cell integrity by withstanding internal turgor pressure. During cell growth, PG endopeptidases cleave the crosslinks of the fully closed sacculi, allowing for the incorporation of new glycan strands and expansion of the peptidoglycan mesh. Outer-membrane-anchored NlpI associates with hydrolases and synthases near PG synthesis complexes, facilitating spatially close PG hydrolysis. Here, we present the structure of adaptor NlpI in complex with the endopeptidase MepS, revealing atomic details of how NlpI recruits multiple MepS molecules and subsequently influences PG expansion. NlpI binding elicits a disorder-to-order transition in the intrinsically disordered N-terminal of MepS, concomitantly promoting the dimerization of monomeric MepS. This results in the alignment of two asymmetric MepS dimers respectively located on the two opposite sides of the dimerization interface of NlpI, thus enhancing MepS activity in PG hydrolysis. Notably, the protein level of MepS is primarily modulated by the tail-specific protease Prc, which is known to interact with NlpI. The structure of the Prc-NlpI-MepS complex demonstrates that NlpI brings together MepS and Prc, leading to the efficient MepS degradation by Prc. Collectively, our results provide structural insights into the NlpI-enabled avidity effect of cellular endopeptidases and NlpI-directed MepS degradation by Prc.
摘要：
肽聚糖（PG）囊围绕细胞质膜，通过承受内部膨胀压力保持细胞的完整性。在细胞生长过程中,PG内肽酶切割完全封闭的囊的交联，允许新的聚糖链的掺入和肽聚糖网的扩展。外膜锚定的NlpI与PG合成复合物附近的水解酶和合酶相关，促进空间接近PG水解。这里,我们提出了与内肽酶MepS复合的衔接子NlpI的结构，揭示NlpI如何招募多个MepS分子并随后影响PG扩展的原子细节。NlpI结合在MepS的固有无序N端引发无序到有序的转变，同时促进单体MepS的二聚化。这导致分别位于NlpI的二聚化界面的两个相对侧的两个不对称MepS二聚体的排列，从而增强PG水解中的MepS活性。值得注意的是,MepS的蛋白质水平主要由尾部特异性蛋白酶Prc调节，已知与NlpI相互作用。Prc-NlpI-MepS复合物的结构表明NlpI将MepS和Prc结合在一起，导致Prc有效的MepS降解。总的来说，我们的结果提供了有关Prc对细胞内肽酶的NlpI使能亲合力效应和NlpI指导的MepS降解的结构见解。
