2P87

Crystal structure of the C-terminal domain of C. elegans pre-mRNA splicing factor Prp8

Summary for 2P87

• Entry DOI: 10.2210/pdb2p87/pdb
• Descriptor: Pre-mRNA-splicing factor Prp8 (2 entities in total)
• Functional Keywords: alpha-beta, splicing
• Biological source: Caenorhabditis elegans
• Cellular location: Nucleus (By similarity): P34369
• Total number of polymer chains: 1
• Total formula weight: 31197.04

Authors

Zhang, L.,Shen, J.,Guarnieri, M.T.,Heroux, A.,Yang, K.,Zhao, R. (deposition date: 2007-03-21, release date: 2007-05-22, Last modification date: 2024-02-21)

Primary citation

Zhang, L.,Shen, J.,Guarnieri, M.T.,Heroux, A.,Yang, K.,Zhao, R.
Crystal structure of the C-terminal domain of splicing factor Prp8 carrying retinitis pigmentosa mutants
Protein Sci., 16:1024-1031, 2007

PubMed Abstract: Prp8 is a critical pre-mRNA splicing factor. Prp8 is proposed to help form and stabilize the spliceosome catalytic core and to be an important regulator of spliceosome activation. Mutations in human Prp8 (hPrp8) cause a severe form of the genetic disorder retinitis pigmentosa, RP13. Understanding the molecular mechanism of Prp8's function in pre-mRNA splicing and RP13 has been hindered by its large size (over 2000 amino acids) and remarkably low-sequence similarity with other proteins. Here we present the crystal structure of the C-terminal domain (the last 273 residues) of Caenorhabditis elegans Prp8 (cPrp8). The core of the C-terminal domain is an alpha/beta structure that forms the MPN (Mpr1, Pad1 N-terminal) fold but without Zn(2+) coordination. We propose that the C-terminal domain is a protein interaction domain instead of a Zn(2+)-dependent metalloenzyme as proposed for some MPN proteins. Mapping of RP13 mutants on the Prp8 structure suggests that these residues constitute a binding surface between Prp8 and other partner(s), and the disruption of this interaction provides a plausible molecular mechanism for RP13.

PubMed: 17473007
DOI: 10.1110/ps.072872007

Experimental method

X-RAY DIFFRACTION (2.3 Å)