User:Olsen-in-HD/sandbox/FtsK

= FtsK =

Structure
FtsK is a transmembrane protein composed of three domains: FtsKN, FtsKL, and FtsKC. The FtsKN domain is embedded in the cellular membrane by four transmembrane α-helices. The FtsKL domain extends from the membrane into the cytoplasm. This linking domain varies in length across many bacteria. Found at the cytoplasmic end of the linker domain, the FtsKC segment of the protein is responsible for enabling the activity of the Xer recombination system upon the formation of a chromosome dimer.

Additionally, the FtsKC domain is composed of three subdomains: α, β, and γ. The α and β subunits aggregate to form a hexamer that possesses the ability to translocate DNA through ATP hydrolysis. The ATP hydrolysis sites are found on the β subunits of the hexamer. The γ domain is responsible for the control of the hexamer. It mediates the attachment of the hexamer to double-stranded DNA, controls the directionality of the translocase, and initiates chromosome dimer segregation.

The dif site
The dif site is found on at the intersection between the monomers of the chromosome dimer. It corresponds to where chromosomal replication ceased and is also the site of Xer mediated segregation. Translocation of the FtsKC hexamer stops when it reaches the location of the Xer recombinase complex that is associated with the dif site.

Binding Site
Guanosine rich areas of DNA, which are found at the ends of the dif region, are the sites of translocation initiation. These sites are referred to as KOPS motifs. Upon binding a KOPS motif, the FtsK hexamer forms and proceeds towards the dif region. Movement toward the dif region is facilitated by the polarity of the KOPS motif.

Translocation
There are three proposed mechanisms of DNA translocation: the rotary inchworm, the staircase, and the revolution mechanism. The rotary inchworm mechanism involves two points of contact between DNA and the FtsKC hexamer. These points of contact correspond to a α and a β subunit. A conformational change in the α subunit can cause the DNA to shift. This shift is followed by a conformational change in the β subunit (which also causes the DNA to move). The repeated conformational changes lead to the translocation of DNA.

Conversely, the staircase mechanism see the α and β subunits of the hexamer interacting with the double-stranded DNA in a sequential manner. Conformational changes in each subunit cause movement in the spatial position of the DNA strand. Additionally, the revolution mechanism entails the passing of DNA through a channel formed by the hexameric FtsKC domain. In general, the chromosome dimer is translocated so that the site of resolution is near the divisome and so one copy of the genetic material ends up in each daughter cell.

Recombinase (Xer D) activation
The recombination apparatus is made up of four monomers, two being Xer D and two being Xer C, that belong to a family of tyrosine recombinases. The interaction of Xer D and the γ subunit of FtsKC results in the activation of the recombinase. Contact between Xer D and the γ subunit is facilitated by the translocation of DNA. Specifically, translocation stops when the FtsKc hexamer reaches the dif site.

Role in cell division
FtsK has been shown to be a part of the divisisome of bacteria. FtsKN is thought to both stabilize the septum and aid in the recruitment of other proteins to the site of cell division. Studies have shown that part of the FtsK­N domain (which is in the periplasm) is involved in the construction of the cell wall.