8ZAY

Crystal structure of Fab from mouse monoclonal antibody 4A9 against Aquifex aeolicus RseP PDZ tandem

Summary for 8ZAY

• Entry DOI: 10.2210/pdb8zay/pdb
• Descriptor: VH-CH1 region of antibody of anti-RseP orthologue from A aeolicus, Light chain of antibody of anti-RseP orthologue from A aeolicus, ZINC ION, ... (4 entities in total)
• Functional Keywords: antibody, protein binding
• Biological source: Mus musculus; More
• Total number of polymer chains: 4
• Total formula weight: 96854.91

Authors

Adachi, Y.,Nogi, T. (deposition date: 2024-04-25, release date: 2025-03-05, Last modification date: 2025-03-12)

Primary citation

Asahi, K.,Hirose, M.,Aruga, R.,Shimizu, Y.,Tajiri, M.,Tanaka, T.,Adachi, Y.,Tanaka, Y.,Kaneko, M.K.,Kato, Y.,Akashi, S.,Akiyama, Y.,Hizukuri, Y.,Kato, T.,Nogi, T.
Cryo-EM structure of the bacterial intramembrane metalloprotease RseP in the substrate-bound state.
Sci Adv, 11:eadu0925-eadu0925, 2025

PubMed Abstract: Site-2 proteases (S2Ps), conserved intramembrane metalloproteases that maintain cellular homeostasis, are associated with chronic infection and persistence leading to multidrug resistance in bacterial pathogens. A structural model of how S2Ps discriminate and accommodate substrates could help us develop selective antimicrobial agents. We previously proposed that the S2P RseP unwinds helical substrate segments before cleavage, but the mechanism for accommodating a full-length membrane-spanning substrate remained unclear. Our present cryo-EM analysis of RseP (RseP) revealed that a substrate-like membrane protein fragment from the expression host occupied the active site while spanning a transmembrane cavity that is inaccessible via lateral diffusion. Furthermore, in vivo photocrosslinking supported that this substrate accommodation mode is recapitulated on the cell membrane. Our results suggest that the substrate accommodation by threading through a conserved membrane-associated region stabilizes the substrate-complex and contributes to substrate discrimination on the membrane.

PubMed: 40009668
DOI: 10.1126/sciadv.adu0925

Experimental method

X-RAY DIFFRACTION (2.3 Å)