Abstract
Salmonella typhimuriumis responsible for over 35% of all foodborne illness related hospitalizations in the United States. This Gram-negative bacteriumpossesses an inner and an outer membrane (OM), the latter allowingits survival and replication within host tissues. During infection, OM is remodeled by transport of glycerophospholipids across the periplasm and into the OM. Increased levels of cardiolipin in the OM were observed upon PhoPQ activation and led to the discovery of YejM; an inner membrane protein essential for cell growth involved in cardiolipin binding and transport to the OM. Another protein that might be playing a role in cardiolipin transport is YejL, as its gene is localized upstream of yejm on the same operon. Here we report how YejM was engineered to facilitate crystal growth and X-ray diffraction analysis. Furthermore, we present for the first time that YejL is a ligand for YejM. Successful structure determination of YejM and YejL will help us understand how they interact and how YejM facilitates cardiolipin transport to the OM. Ultimately, yejm, being an essential gene, may lead to new drug targets inhibiting the pathogenic properties of S. typhimurium.
Highlights
Salmonella typhimurium is a Gram-negative bacterium responsible for over 35% of all foodborne illness-related hospitalizations in the United States (Painter et al, 2013)
YejM is comprised of 586 amino acids forming five predicted N-terminal transmembrane helices, followed by an arginine-rich periplasmic random coil linker region, and a C-terminal periplasmic domain (Figure 1A), and it was shown that YejM associates as a tetramer in solution (Dalebroux et al, 2015)
We aim to solve the co-crystal structure of YejL and/or cardiolipin bound to YejM
Summary
Salmonella typhimurium is a Gram-negative bacterium responsible for over 35% of all foodborne illness-related hospitalizations in the United States (Painter et al, 2013). Increased levels of cardiolipin in S. typhimurium OM were observed upon PhoPQ regulator activation (Dalebroux et al, 2014). The inner membrane protein YejM was shown to bind cardiolipin and be involved in OM formation (Dalebroux et al, 2015). YejM is comprised of 586 amino acids forming five predicted N-terminal transmembrane helices, followed by an arginine-rich periplasmic random coil linker region, and a C-terminal periplasmic domain (Figure 1A), and it was shown that YejM associates as a tetramer in solution (Dalebroux et al, 2015). The arginine-rich linker region and periplasmic globular domain of YejM were shown to bind cardiolipin and are required for OM remodeling and cell growth (Dalebroux et al, 2015). The molecular mechanism of the interplay between PhoPQ system and YejM, and how cardiolipin molecules are transported to the OM, need further structural and functional investigation
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