Structural basis for recruitment of peptidoglycan endopeptidase MepS by lipoprotein NlpI.
Journal
Nature communications
Journal Volume
15
Journal Issue
1
Start Page
article 5461
ISSN
2041-1723
Date Issued
2024-06-27
Author(s)
Wang, Shen
Huang, Chun-Hsiang
Lin, Te-Sheng
Yeh, Yi-Qi
Fan, Yun-Sheng
Wang, Si-Wei
Tseng, Hsi-Ching
Huang, Shing-Jong
Chang, Yu-Yang
Jeng, U-Ser
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.
SDGs
Type
journal article