structure of transposases
A general pattern for the functional organisation of Tpases appears to be
emerging from the increasing number which have been analysed.Many can be divided into topologically distinct structural
domains and, although several regions of the protein may contribute to a given
function, the isolated domains themselves often exhibit a distinct function. The
sequence-specific DNA binding activities of the proteins are generally located
in the N-terminal region while the catalytic domain is often localised towards
the C-terminal end: IS1(Machida & Machida, 1989),(Zerbib, et al., 1990); IS30 (Stalder, et al., 1990); Mu, see (Lavoie & Chaconas, 1996); Tn3 (Maekawa, et al., 1993, Maekawa & Ohtsubo,
1994); IS50 (Wiegand & Reznikoff, 1994); IS903 (Tavakoli, et al., 1997); IS911 (Polard, et al., 1996); for review see (Haren, et al., 1999) (Fig 1.27.1). One
functional interpretation of this arrangement for prokaryotic elements is that
it may permit interaction of a nascent protein molecule with its target
sequences on the IS thus coupling expression and activity. This notion is
reinforced by the observation that the presence of the C-terminal region of the IS50, IS10 and IS911 Tpases appears to mask the DNA binding domain and reduce
binding activity (Weinreich, et al., 1994), (Jain & Kleckner, 1993), possibly by masking the DNA binding domain. This arrangement
might favor activity of the protein in cis, a property shared by several Tpases
(see Activity in cis below). Similar masking appears to occur with the IS1 (D. Zerbib and
M.C., unpublished) and the IS911 Tpases (Haren, et al., 1998), (Normand, et al., 2001)(Normand, et al., 2001). In several cases these domains are
assembled into a single protein from consecutive orfs by translational
frameshifting (Programmed translational
frameshifting). In the case of IS911, it has been demonstrated
that transposase binding to the IS ends occurs as the protein is translated (Duval-Valentin & Chandler, 2011).
One exception to this is the transposase of the IS110 family which encodes a DEDD
transposase closely related to the RuvC Holiday resolvase (see (Buchner, et al., 2005) and (Choi, et al.,
2003)) and in which the catalytic domain appears to precede the DNA
additional characteristic of some, if not all, Tpases is the capacity to
generate multimeric forms essential for their activity (see (Haren, et al.,
1999)). This is true of prokaryotic elements such as bacteriophage Mu
(see (Chaconas, et al.,
1996)), IS50 (Weinreich, et al., 1994), IS911 (Haren, et al., 1998), (Haren, et al.,
2000), (Normand, et al., 2001), IS608 and ISDra2 (Ronning, et al., 2005, Hickman, et al., 2010) (but apparently
not IS10 (Bolland & Kleckner, 1996), and of
eukaryotic elements such as the retroviruses (see (Katz
& Skalka, 1994),(Jones, et al., 1992); (Bao, et al., 2002, Faure, et al.,
2005)) whose integrase (IN) (transposase) appears to be a dimer of dimers both with and without DNA bound (Bao, et al.,
2003); (Ren, et al., 2007); (Hare, et al.,
2009); (Michel, et al., 2009) as does the purified P element transposase (Tang, et al.,
2007), the mariner-like element, Mos1 (Lohe, et al., 1996,Richardson, 2007, Richardson, et al., 2009) and hermes (which is a hexamer) (Hickman, et al.,
2005, Hickman, et al., 2014).
With the results of an increasing number of structural studies of these types
of enzyme, it will be of great interest to compare the overall similarities of
equivalent functional domains as has been recently possible with the catalytic
domains of retroviral integrases , Mu transposase and other polynucleotidyl
transferases such as the Holiday resolvase, RuvC and RnaseH (see (Rice, et al., 1996) and (Grindley & Leschziner, 1995)
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