4R3E

Structure of the spliceosomal peptidyl-prolyl cis-trans isomerase Cwc27 from Homo sapiens

Summary for 4R3E

• Entry DOI: 10.2210/pdb4r3e/pdb
• Related: 2HQ6 4R3F
• Descriptor: Peptidyl-prolyl cis-trans isomerase CWC27 homolog, GLYCEROL (3 entities in total)
• Functional Keywords: cyclophilin-type ppiase, nucleus, isomerase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 20409.83

Authors

Ulrich, A.,Wahl, M.C. (deposition date: 2014-08-15, release date: 2014-11-19, Last modification date: 2023-09-20)

Primary citation

Ulrich, A.,Wahl, M.C.
Structure and evolution of the spliceosomal peptidyl-prolyl cis-trans isomerase Cwc27.
Acta Crystallogr.,Sect.D, 70:3110-3123, 2014

PubMed 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.

PubMed: 25478830
DOI: 10.1107/S1399004714021695

Experimental method

X-RAY DIFFRACTION (2 Å)