2p8r
From Proteopedia
Crystal structure of the C-terminal domain of C. elegans pre-mRNA splicing factor Prp8 carrying R2303K mutant
Overview
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.
About this Structure
2P8R is a Single protein structure of sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA.
Reference
Crystal structure of the C-terminal domain of splicing factor Prp8 carrying retinitis pigmentosa mutants., Zhang L, Shen J, Guarnieri MT, Heroux A, Yang K, Zhao R, Protein Sci. 2007 Jun;16(6):1024-31. Epub 2007 May 1. PMID:17473007 Page seeded by OCA on Sun May 4 12:37:02 2008
