Preliminary study of the spatial structural and functional changes of dystrophin after exon-3 deletion.
- Author:
Ying-Yin LIANG
1
;
Cheng ZHANG
;
Song-Lin CHEN
;
Shan-Wei FENG
Author Information
- Publication Type:Journal Article
- MeSH: Dystrophin; chemistry; genetics; metabolism; Exons; genetics; Humans; Models, Molecular; Muscular Dystrophy, Duchenne; genetics; metabolism; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Sequence Deletion; Structure-Activity Relationship
- From: Journal of Southern Medical University 2008;28(6):938-941
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the structural and functional changes of dystrophin molecule after exon 3 deletion.
METHODSThree-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.
RESULTSTorsion 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.
CONCLUSIONExon 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.