Читать книгу Snyder and Champness Molecular Genetics of Bacteria - Tina M. Henkin - Страница 95

Surprisingly, the chromosomes of E. coli and other Enterobacteriaceae do not have a recognizable Par-like system, despite the fact that plasmids with ParAB/parS systems are common in Enterobacteriaceae, and it seems likely that another system is responsible for the active partitioning of the chromosomes. Work in E. coli suggests that an incompletely understood system that hinges on large independently organizing regions called macrodomains functions in Enterobacteriaceae. Macrodomains (MD) were first established as large regions in the E. coli chromosome where recombination between two sites within a given macrodomain region occurs at a much greater frequency than outside the macrodomain region (see Valens et al. 2004, Suggested Reading). These regions localize to a specific subregion within the larger nucleoid and show individualized segregation properties. Four regions were identified as having these properties, one encompassing the origin region (Ori-MD), one encompassing the terminus region (Ter-MD), and two regions to the right (Right-MD) and left (Left-MD) of the terminus region (Figure 1.21). Two regions surrounding the origin macrodomain appear to not be as structured. Extensive molecular details exist for the Ter macrodomain, but little is known about the other macrodomain regions.

Figure 1.21 The E. coli chromosome has four structured regions called macrodomains (MDs) that aid in segregation of the chromosome. (A) Approximate genetic positions of the Ori-MD, the Right- and Left-MD, the Ter-MD, and the two unstructured regions of the E. coli chromosome. The Ter-MD is the best understood and is organized by the MatP protein via an association with its matS sites across the terminus region of the chromosome. The tidL and tidR sites, which are recognized by the YfbV protein (not shown), constrain the MatP protein from extending outside this region. (B) MatP compacts and localizes the Ter-MD through an association with ZapB (not shown), which is localized around the FtsZ ring region. The Ori-MD is organized via an association of the MaoP protein with a single site near the origin, maoS, via an unknown mechanism. The molecular mechanism responsible for organizing the Right- and Left-MDs and any associated proteins is unknown.

The Ter macrodomain: MatP and matS. The molecular basis for the Ter macrodomain involves a series of 23 matS sites found across an 800-kb region that are recognized by the protein MatP (see Mercier et al., Suggested Reading). MatP-matS complexes compact this region where they also associate with a specific set of proteins localized at the center, facilitating the process of orderly cell division (see below) (Figure 1.21B). The structure formed with MatP-matS appears to be constrained from spreading by two sites (tidL and tidR) which interact with a partner protein suggested to associate with the cell membrane (Figure 1.21A). Presumably, the MatP-matS system would coordinate the segregation of the terminus region as a late step in chromosome segregation. The molecular basis for the left and right macrodomains remains unknown.

The origin macrodomain: maoS and MaoP. Recombination studies were used to establish two important players in the origin macrodomain (see Valens et al. 2016, Suggested Reading). The explanation for the origin macrodomain is less clear, but appears to involve a single cis-acting site called maoS, found about 22 kb away from oriC, that is recognized by the MaoP protein (Figure 1.20). It remains unclear how a single site allows the formation of this large macrodomain or how it would function. The MaoP-maoS system is functionally distinct from the ParAB-parS partitioning systems found in plasmids and most other bacterial chromosomes, and placing the MaoP-maoS system onto a plasmid does not recapitulate the segregation found with the origin region, suggesting that important pieces are still missing from this story. A 25-bp site called migS was identified for its role in orienting the origin region within the larger nucleoid, but any role this site plays in segregation or any trans-acting factor that works with this site has yet to be identified (see Yamaichi and Niki, Suggested Reading).

Interestingly, a number of systems found in E. coli and other enteric bacteria appear to have coevolved: MatP/matS, MaoP/maoS, MukBEF, SeqA, and Dam methyltransferase along with a number of other proteins are only found in this subgroup of bacteria (see Brézellec et al., Suggested Reading). It is unclear how these systems functionally replace the ParAB-parS system found in most bacteria, and it will be interesting to discover how the systems relate and function in Enterobacteriaceae.