8XUD

Crystal structure of adaptor NlpI in complex with endopeptidase MepS and PDZ-protease Prc

Summary for 8XUD

• Entry DOI: 10.2210/pdb8xud/pdb
• Descriptor: Lipoprotein NlpI, Tail-specific protease, Murein DD-endopeptidase MepS/Murein LD-carboxypeptidase, ... (6 entities in total)
• Functional Keywords: hydrolases, lipoprotein, protease, protein complex, protein binding, substrate degradation
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 10
• Total formula weight: 302612.82

Authors

Tzeng, S.R.,Wang, S.,Huang, C.H. (deposition date: 2024-01-12, release date: 2024-06-05, Last modification date: 2024-12-18)

Primary citation

Wang, S.,Huang, C.H.,Lin, T.S.,Yeh, Y.Q.,Fan, Y.S.,Wang, S.W.,Tseng, H.C.,Huang, S.J.,Chang, Y.Y.,Jeng, U.S.,Chang, C.I.,Tzeng, S.R.
Structural basis for recruitment of peptidoglycan endopeptidase MepS by lipoprotein NlpI.
Nat Commun, 15:5461-5461, 2024

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.

PubMed: 38937433
DOI: 10.1038/s41467-024-49552-y

Experimental method

X-RAY DIFFRACTION (3.49 Å)