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the relative orientation between the dimerization and external subdomains
(
Fig. 4
). In turn, this conformational change alters the orientation of helix
a
E
and the
a
E-
b
8 loop that in the structure of
E. coli
MutL-CTD includes an
additional helix, while in the structures of
B. subtilis
and
N. gonorrhoeae
,
MutL-CTD adopts an extended conformation. Collectively, the conformational
changes around helix
a
A shape the endonuclease site of the protein (see
below).
Recently, the structure of the C-terminal domain of hMLH1 has also been
determined (PDB ID: 3RBN). Human MLH1 is the common subunit in
the hMutL
a
, hMutL
b
, and hMutL
g
heterodimers; however, when produced
in the absence of its functional partners, it can also form stable homodimers
(J. Wong and A. Guarn
´
, unpublished results). The structure of the C-terminal
domain of MLH1 is significantly different from those of other MutL homologs
F
IG
. 5. Crystal structure of the dimerization domain of human MLH1. Orthogonal views of
the MLH1 dimer (residues 479-756) with one protomer colored as a rainbow from the N (blue) to
the C terminus (red) with the secondary structure elements labeled. The other protomer is shown
as a white ribbon with the N-terminal extension—found in MLH1, but not in other MutL
homologs—shown in blue. The location of the insertions setting apart MLH1 from other MutL
homologs are marked with black arrows and the putative PCNA-binding motif is highlighted in
purple. The view on the bottom panel resembles the orientation shown in
Fig. 4
.
