8VJL

SpoIVFB:pro-sigmaK complex

Summary for 8VJL

• Entry DOI: 10.2210/pdb8vjl/pdb
• EMDB information: 43288
• Descriptor: Stage IV sporulation protein FB, RNA polymerase sigma factor, Lauryl Maltose Neopentyl Glycol, ... (4 entities in total)
• Functional Keywords: spoivfb, sigmak, s2p, site-2-protease, protease, membrane protein
• Biological source: Bacillus subtilis subsp. subtilis str. 168; More
• Total number of polymer chains: 8
• Total formula weight: 213728.84

Authors

Orlando, M.A.,Pouillon, H.J.T.,Mandal, S.,Kroos, L.,Orlando, B.J. (deposition date: 2024-01-07, release date: 2024-10-02, Last modification date: 2024-10-30)

Primary citation

Orlando, M.A.,Pouillon, H.J.T.,Mandal, S.,Kroos, L.,Orlando, B.J.
Substrate engagement by the intramembrane metalloprotease SpoIVFB.
Nat Commun, 15:8276-8276, 2024

PubMed Abstract: S2P intramembrane metalloproteases regulate diverse signaling pathways across all three domains of life. However, the mechanism by which S2P metalloproteases engage substrates and catalyze peptide hydrolysis within lipid membranes has remained elusive. Here we determine the cryo-EM structure of the S2P family intramembrane metalloprotease SpoIVFB from Bacillus subtilis bound to its native substrate Pro-σ. The structure and accompanying biochemical data demonstrate that SpoIVFB positions Pro-σ at the enzyme active site through a β-sheet augmentation mechanism, and reveal key interactions between Pro-σ and the interdomain linker connecting SpoIVFB transmembrane and CBS domains. The cryo-EM structure and molecular dynamics simulation reveal a plausible path for water to access the membrane-buried active site of SpoIVFB, and suggest a possible role of membrane lipids in facilitating substrate capture. These results provide key insight into how S2P intramembrane metalloproteases capture and position substrates for hydrolytic proteolysis within the hydrophobic interior of a lipid membrane.

PubMed: 39419996
DOI: 10.1038/s41467-024-52634-6

Experimental method

ELECTRON MICROSCOPY (3.5 Å)