title: Structural bioinformatics of the human spliceosomal proteome.
abstract: In this work, we describe the results of a comprehensive structural bioinformatics analysis of the spliceosomal proteome. We used fold recognition analysis to complement prior data on the ordered domains of 252 human splicing proteins. Examples of newly identified domains include a PWI domain in the U5 snRNP protein 200K (hBrr2, residues 258-338), while examples of previously known domains with a newly determined fold include the DUF1115 domain of the U4/U6 di-snRNP protein 90K (hPrp3, residues 540-683). We also established a non-redundant set of experimental models of spliceosomal proteins, as well as constructed in silico models for regions without an experimental structure. The combined set of structural models is available for download. Altogether, over 90% of the ordered regions of the spliceosomal proteome can be represented structurally with a high degree of confidence. We analyzed the reduced spliceosomal proteome of the intron-poor organism Giardia lamblia, and as a result, we proposed a candidate set of ordered structural regions necessary for a functional spliceosome. The results of this work will aid experimental and structural analyses of the spliceosomal proteins and complexes, and can serve as a starting point for multiscale modeling of the structure of the entire spliceosome.
authors.affiliation: Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Warsaw PL-02-109, Poland.
authors.forename: Iga
authors.initials: I
authors.lastname: Korneta
authors.forename: Marcin
authors.initials: M
authors.lastname: Magnus
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry; D019295:Computational Biology; D016829:Giardia lamblia; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry*; D020365:RNA Helicases / Q000737:chemistry; D012326:RNA Splicing; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000737:chemistry; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000737:chemistry; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry*; D016415:Sequence Alignment; D017381:Spliceosomes / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry; D016335:Zinc Fingers
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; C108507:PRPF3 protein, human; C115374:PRPF8 protein, human; D020543:Proteome; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D025801:Ubiquitin; C088049:splicing factor 3a; D020365:RNA Helicases