Structure and evolution of the spliceosomal peptidyl-prolyl cis-trans isomerase Cwc27.
A.Ulrich,
M.C.Wahl.
ABSTRACT
Cwc27 is a spliceosomal cyclophilin-type peptidyl-prolyl cis-trans isomerase
(PPIase). Here, the crystal structure of a relatively protease-resistant
N-terminal fragment of human Cwc27 containing the PPIase domain was determined
at 2.0 Å resolution. The fragment exhibits a C-terminal appendix and resides
in a reduced state compared with the previous oxidized structure of a similar
fragment. By combining multiple sequence alignments spanning the eukaryotic tree
of life and secondary-structure prediction, Cwc27 proteins across the entire
eukaryotic kingdom were identified. This analysis revealed the specific loss of
a crucial active-site residue in higher eukaryotic Cwc27 proteins, suggesting
that the protein evolved from a prolyl isomerase to a pure proline binder.
Noting a fungus-specific insertion in the PPIase domain, the 1.3 Å resolution
crystal structure of the PPIase domain of Cwc27 from Chaetomium thermophilum was
also determined. Although structurally highly similar in the core domain, the C.
thermophilum protein displayed a higher thermal stability than its human
counterpart, presumably owing to the combined effect of several amino-acid
exchanges that reduce the number of long side chains with strained conformations
and create new intramolecular interactions, in particular increased
hydrogen-bond networks.
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