[Preliminary study of the spatial structural and functional changes of dystrophin after exon-3 deletion].
OBJECTIVE
To explore the structural and functional changes of dystrophin molecule after exon 3 deletion.


METHODS
Three-dimensional models of dystrophin comprising the major domains were established before and after exon 3 deletion using SWISS-MODEL server. The motifs and structural domains of dystrophin after exon 3 deletion were searched in Pfam database, and the crystal structure of the actin-binding domain in the dystrophin molecule was analyzed using Rasmol software.


RESULTS
Torsion of the N-terminal actin-binding domain occurred in the dystrophin molecule after deletion of exon 3. Homology analysis based on Pfam database searches indicated that following exon 3 deletion, the Bit score of the first calponin homology (CH1) domain was decreased from 108 to 36.5 while its expectation value increased from 2.3e-9 to 8.1e-8. The deletion also resulted in the absence of the spiral region C from the CH1 domain.


CONCLUSIONS
Exon 3 deletion in the dystrophin-coding sequence decreases the stability of CH1 domain and prevents the formation of the junction interface where dystrophin binds to actin. The bioinformatics approach provides a new alternative for investigation of the pathogenesis of DMD pathogenesy investigation.
Liang
Ying-Yin
YY
Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, China.
Zhang
Cheng
C
Chen
Song-Lin
SL
Feng
Shan-Wei
SW
D016189:Dystrophin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
D016189:Dystrophin