Ii this paper we carry out a structural genomics analysis of known alternative splicing events and show that threading is a valid approach to model structures of alternatively spliced variants. We collect 3-D structures of proteins with know translated splicing products from PDB and further expand the dataset with high quality models generated with threading approach. Our analysis shows that splicing events have a strong preference for non-regular secondary structure elements and tend to avoid buried residues. Those observations suggest evolutionary constrains exist for locations of splicing in the context of 3-D environment. We then show that majority of substitutions in splicing events share high structural similarity and splicing events also tend to remove entire domain and avoid exposing hydrophobic cores when part of a domain was removed. Those observations support the notion that majority of splicing isoforms adopt same fold as full-length protein despite sequence substitutions and deletions. This principle was then utilized to generate high quality structures of splicing variants that could be a valuable resource for studying their structures and functions and may provide new insights into pathogenesis of related diseases.
[1]
D. Black.
Mechanisms of alternative pre-messenger RNA splicing.
,
2003,
Annual review of biochemistry.
[2]
Pierre Hainaut,et al.
p53 protein variants: structural and functional similarities with p63 and p73 isoforms
,
2004,
Oncogene.
[3]
J. Venables.
Aberrant and Alternative Splicing in Cancer
,
2004,
Cancer Research.
[4]
H. Taubert,et al.
Alternative and aberrant splicing of MDM2 mRNA in human cancer.
,
2002,
Cancer cell.
[5]
J. Castle,et al.
Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays
,
2003,
Science.