Structures for four neisserial Slam-dependent SLPs have been solved by X-ray crystallography and NMR (Figure ?(Figure5).5). involved Vorasidenib in several important cellular pathways for nutrient acquisition, cellular adhesion and stress response (Zckert, 2014; Szewczyk and Collet, 2016; Wilson and Bernstein, 2016). The discovery of SLPs in different bacteria has raised questions regarding the biosynthetic pathway used by these proteins for their synthesis and transport to the surface. SLPs are Cd14 synthesized in the cytoplasm and transported to the periplasm by the Sec or Tat machinery based on the signal sequence present on the SLPs (Chatzi et al., 2013). Once in the periplasm, three enzymes in the inner membrane process the SLPs by cleaving the signal sequence and attaching three fatty acyl chains to the N-terminal cysteine residue (Szewczyk and Collet, 2016). Upon lipidation, most SLPs are transported across the periplasm to the inner leaflet of the outer membrane through the Lol system (Okuda and Tokuda, 2011). However, there are a few exceptions to this rule, including pullulanase that avoids the Lol system and moves to the surface through the Type-II secretion system (D’Enfert et al., 1987). Additionally, in sp., SLPs are proposed to require a periplasmic holding chaperone that prevents premature folding of SLPs before reaching the outer membrane (Chen and Zckert, 2011; Zckert, 2014). Upon insertion into the outer membrane, the translocation systems required for the movement Vorasidenib of SLPs across the outer membrane remain poorly characterized. The first SLP for which the export pathway was characterized was pullulanase in sp. that utilizes the Type II secretion system (D’Enfert et al., 1987). More recent studies have shown that NalP (a neisserial SLP) functions as a Type Va autotransporter secretion system (Van Ulsen et al., 2003), while BamC (Webb et al., 2012) and RscF (Cho et al., 2014; Konovalova et al., 2014) in use the Bam complex to move across the outer membrane. Functional and mutagenesis studies in sp. (Schulze et al., 2010; Chen and Zckert, 2011) and sp. (Lauber et al., 2016) have shown that the sorting rules used by these SLPs are distinct from other SLPs, indicating that different bacterial species may possess different translocation systems for the delivery of SLPs. Additionally, within sp., distinct SLP export pathways have been reported (Hooda et al., 2017), suggesting that multiple systems for the export of SLPs may exist in a single bacterial species. The SLPs found in the genus are amongst the most extensively studied SLPs. and encode multiple SLPs that are involved in a variety of cellular Vorasidenib pathways critical for survival of neisserial pathogens in humans (Hooda et al., 2017). In autotransporter protease (NalP) (Van Ulsen et al., 2003), anaerobically induced protein A (AniA) (Hoehn and Clark, 1992) and macrophage infectivity potentiator (MIP) (Leuzzi et al., 2005) which play roles in extracellular proteolysis, anaerobic growth and intracellular survival respectively. These SLPs have been shown to bind to Vorasidenib different human factors and atomic resolution full-length or partial structures of these SLPs have aided in understanding their mechanism of action (Hooda et al., 2017). Recently, we described a family of outer membrane proteins called Slam or Surface lipoprotein assembly modulator that is essential for surface display of a subset of neisserial SLPs (Hooda et al., 2016). contains two Slam proteins: Slam1.