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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Guo, Jun-tao Xu, Ying Wang, Peng Hicks, Chindo Yan, Bo |
| Description | Author Affiliation: Wang P ( Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA 30622, USA.); |
| Abstract | Alternative splicing is a sophisticated nuclear process that regulates gene expression. It represents an important mechanism for enhancing the functional diversity of proteins. Our current knowledge of alternatively spliced variants is derived mainly from mRNA transcripts, and very little is known about their protein tertiary structures. We carried out a large-scale analysis of known alternatively spliced variants at both protein sequence and structure levels and have shown that threading is, in general, a viable approach for modeling structures of alternatively spliced variants. An examination of alternative splicing at the protein sequence level revealed that the size of splicing events follows the power law distribution and the majority of splicing isoforms harbor only one or two alternations. We examined alternative splicing in the context of protein 3D structures and found that the boundaries of alternative splicing events generally happen in coil regions of secondary structures and exposed residues and the majority of the sequences involved in splicing are located on the surface of proteins. In light of these findings, we then proceeded to demonstrate that threading represents a useful tool for structure prediction of alternative splicing isoforms and addressed the fold stability issue of threading-based structure prediction by molecular dynamics simulation. Our analysis and the insights gained have helped to establish a viable method for structure prediction of alternatively spliced isoforms at the genome scale. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 52 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alternative Splicing Genomics Proteins Chemistry Proteomics Computational Biology Genome Genome, Human Models, Molecular Protein Conformation Protein Isoforms Protein Structure, Secondary RNA Splicing RNA, Messenger Metabolism Time Factors Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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