2.5) Fis
Fis for Factor of Inversion Stimulation, a 98-amino-acid
homodimeric protein (11.4 kDa), was named and first identified for its
role in the G-loop inversion of the bacteriophage Mu (Koch and Kahmann,
1986). Like the other NAPs, Fis is involved in the organisation and the
maintenance of the nucleoid structure (Table 1 ) (Schneider,
2001). It is composed of four helices and a β-hairpin arm in the
N-terminal domain that facilitates DNA inversion. It bends DNA up to
90°, stabilising DNA looping and aiding in DNA compaction (Skokoet al. , 2006). Fis binds as a homodimer to regulate the
transcription of topoisomerases (topA and gyrB), thereby
affecting the level of supercoiling of the cell, i.e. is the over- or
under-winding of the DNA double helix relative to the relaxed state
(Ohniwa et al. , 2006). It binds to a highly degenerate 15-bp
consensus sequence (GnnYAnnnnTRnnC, where Y is T or C and R is A or G)
(Stella, Cascio and Johnson, 2010). Fis is one of the most abundant NAPs
during the exponential phase (over 60,000 proteins per cell) and drops
drastically upon entry into the stationary phase, to less than 100
copies per cell (Ali Azam et al. , 1999). This growth phase
regulation explains the major role of Fis in the activation of stable
RNA genes, required for rapid bacterial growth (Hirsch and Elliott,
2005; Lautier and Nasser, 2007). Fis abundance also varies depending on
the metabolic state of the cell: for example, high levels of the
alarmone guanosine tetraphosphate ((p)ppGpp) negatively regulatefis expression (Ninnemann, Koch and Kahmann, 1992). A partially
overlapping function between Fis and H-NS should be noted, as Fis also
represses xenogeneic regions of the genome (Karambelkar, Swapna and
Nagaraja, 2012; Amemiya, Schroeder and Freddolino, 2021).