Figure 4. Target T1170, a Holliday junction hexamer (PDB: 7PBR).(A) superposition of two deformed chains versus (B)four undeformed chains in the same frame of reference. The domain that
moves the most with respect to other two is encircled. (C)Grishin plots for the original target split into three domains show the
similarity of results on domains 1, 2 and their combination 12 (left
panel, points close to the diagonal), and the dissimilarity of results
on the combined substructures 13 and 23 and their constituent domains
(middle and right).
In all other targets, except for T1120, T1121 and T1170 discussed above,
chains were largely similar, and the decision on domain splitting was
dictated purely by Grishin plots. Below we discuss three cases of some
of the most difficult domain rearrangements.
Target T1158 is a type IV ABC transporter, which is a common fold (see
review 26). In CASP15,
this protein family was represented by five targets - T1158 (Figure 5A)
and T1158v1-v4, which differ by rigid body movements of the two halves
of the transporter with respect to one another, and no significant
rearrangements within the subunits (Figure 5B). When submitted to domain
parsing programs, T1158 was split in several ways, none of which made
functional sense. The suggested split was either too fragmented (6
domains by DDomain, or 5/8/7 by the top three SWORD assignments) or too
coarse-grained (2 domains by DomainParser: the C-terminal globular
domain (red) in Figure 5A (48-1022) and the rest). We split this target
into two EUs (Figure 5C) reflecting the conformational changes that the
transporter undergoes performing its biological function of opening and
closing gates in bound and unbound states. In other words, evaluation
units for T1158 were defined not from a single structure, but from a set
of structures from the same superfamily. A Grishin plot for the target
(not shown) supports the suggested split.