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.
['Peng Wang', 'Bo Yan', 'Jun-tao Guo', 'Chindo Hicks', 'Ying Xu']
Structural genomics analysis of alternative splicing and its application in modeling structures of alternatively spliced variants