In silico analyses of dystrophin Dp40 cellular distribution, nuclear export signals and structure modeling

Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy) gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids 93LEQEHNNLV101 and 168LLLHDSIQI176 could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here are related to the research article entitled “EF-hand domains are involved in the differential cellular distribution of dystrophin Dp40” (J. Aragón et al. Neurosci. Lett. 600 (2015) 115–120) [1].


a b s t r a c t
Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy) gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids 93 LEQEHNNLV 101 and 168 LLLHDSIQI 176 could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here

Value of the data
Bioinformatics tools permit to search putative dystrophin Dp40 protein domains and/or functions; PSORT II program is an alternative tool to screen for the subcellular localization of Dp40 proteins; NetNES 1.1 server allows to identify putative nuclear export signals of dystrophin Dp40; Comparative modeling analysis between Dp40 and Dp40 mutants identify differences in protein structure.
1. Data, experimental design, materials and methods

Prediction of the subcellular localization of putative Dp40 and mutant proteins
To predict the subcellular localization, the amino acids sequence of Dp40 protein (Protein ID: AGV74356.1) was analyzed using PSORT II software (http://www.genscript.com/psort/psort2.html) [2]. The Dp40 protein was predicted as a cytoplasmic protein while the predicted localization of Dp40n4, carrying changes L93P and L170P (L93/170P) into the EF1 and EF2 hand domains, was nuclear (Table 1). Additional changes are present in Dp40n4 (M288T and D303G); however, none of these changes modified the predictions of the subcellular localization and NES score. Interestingly, the replacement of proline to leucine residues in Dp40n4, either Dp40n4-P93L, Dp40n4-P170L or Dp40n4-P93/170L, was scored as cytoplasmic (Table 1). In addition, the replacement of leucines 93 and 170 to proline residues in Dp40 (Dp40-L93/170P), was predicted to have a nuclear localization (Table 1) which was confirmed by site-directed mutagenesis [1].

Identification of putative nuclear export signals in Dp40 amino acid sequence
To identify possible nuclear export signals (NES), a close analysis of Dp40 and Dp40n4 amino acid sequences was carried out using the NetNES 1.1 server (http://www.cbs.dtu.dk/services/NetNES/) [3].

Comparative modeling analyses between Dp40 and mutant proteins
To identify whether mutations L93P and L170P modify the tertiary structure of Dp40 proteins, structure modeling of Dp40 and Dp40 mutants were analyzed using SWISS-MODEL and I-TASSER programs [4,5]. Fig. 2 shows the tertiary structure modeling of putative Dp40 proteins. Differences are observed between Dp40 and Dp40 mutants as well as among Dp40 mutants.   Comparative modeling of Dp40, Dp40-L93P, Dp40-L170P and Dp40-L93/170P proteins. Structure modeling was carried out using SWISS-MODEL and I-TASSER programs [4,5]. Circles indicate differences between Dp40 and Dp40 mutants. Arrows indicate leucine and/or proline residues 93 and 170 (red).