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Figure 4.
Figure 4. Unique Trans-Acting Residues Characterize the MCM
AAA+ Domain
(A) Model of the MCM hexamer derived as per
Figure 3B showing the location of the composite active site
formed between two AAA+ domains (colored in blue and red).
(B) A close up view of the composite active site showing
residues that have been demonstrated to be critical for ATP
hydrolysis. The composite active site in MCM has unique features
that distinguish the AAA+ modules of these proteins from
classical AAA+ ATPases such as DnaA.
(C) Within the active
site of DnaA (Erzberger et al., 2006), the Walker A and B
motifs, sensor I and sensor II helix, are situated in one
molecule as cis-acting elements, but the critical arginine
finger is a trans-acting residue that is contributed from a
neighboring subunit.
(D) In contrast, the sensor II helix
in MCM functions in trans and is contributed by a neighboring
subunit.
(E–H) This arrangement of trans-acting elements
is similar to that found in viral superfamily III helicases,
such as the papillomavirus E1 helicase (Enemark and Joshua-Tor,
2006) (E). An additional trans-site has been identified by
biochemical analysis of SsoMCM (Moreau et al., 2007) and
consists of a motif containing a highly conserved acidic residue
at the base of PS1BH. Comparison of the structure of the SV40
large T antigen bound to (F) ATP and (G) ADP demonstrates that
this acidic residue orients the arginine finger in response to
the nature of the nucleotide (Gai et al., 2004). Likewise, a
similar, highly conserved acidic residue is located as a
trans-element in MCM (H) where it might similarly affect
intersubunit association in response to nucleotide hydrolysis.
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