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Homology Modeling of a RNP Domain from a Human RNA-binding Protein Homologous to the D. melanogaster Couch Potato Protein

Parag V. Sahasrabudhe (1), Roberto Tejero (1), Yasuhiro Furuichi (2) and Gaetano T. Montelione (1)

(1) Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854.

(2) AGENE Research Institute, Kamakura, 247 Japan.

The RBP-MS gene is located on human chromosome 8 near the Werner's syndrome gene. Different types of RBP-MS arising from different splicing patterns contain an N-terminal common region coded in the first five exons and a C-terminal variable region. An RNA-binding domain is located in the N-terminal common region and contains two consensus RNA-binding sequences RNP1 and RNP2. This RNA-binding domain shows more than 30% sequence homology with the N-terminal RNA-binding domain of the human snRNP U1A protein. Three dimensional structures of snRNP U1A, determined by X-ray crystallography and NMR, are available.

We have recently described an automatic approach for homology modeling using restrained molecular dynamics and simulated annealing procedures (Li et al Protein Sci., In press, 1997). We have employed this approach for constructing a homology model of the RNA-binding domain of RBP-MS. The regions of RBP-MS which are homologous to snRNP U1A were constrained by "homology distance constraints", while the conformation of the non-homologous regions were defined only by a potential energy function. A full energy function without explicit solvent was employed. The effects of misalignment of the unknown and the template sequences were also explored to determine the validity of this homology modeling method.

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