3号外显子缺失后dystrophin蛋白空间结构和功能改变  

Preliminary study of the spatial structural and functional changes of dystrophin after exon-3 deletion

作　　者：梁颖茵[1] 张成[1] 陈松林[1] 冯善伟[2] 

机构地区：[1]中山大学附属第一医院神经内科,广东广州510700 [2]中山大学干细胞与组织工程研究中心,广东广州510700

出　　处：《南方医科大学学报》2008年第6期938-941,共4页Journal of Southern Medical University

基　　金：广东省医学科研基金(A2006177);广东省自然科学基金(06300815)~~

摘　　要：目的探讨3号外显子缺失后营养障碍基因蛋白空间结构和功能的改变及其机制。方法SWISS-MODEL同源模构3号外显子缺失前后营养障碍基因蛋白重要结构区的三维模型。Pafm数据库搜索识别3号外显子缺失后营养障碍基因蛋白的基序和结构域。分析PDB数据库搜索的营养障碍基因肌动蛋白结合区域晶体结构。结果3号外显子缺失后营养障碍基因的氨基端发生扭转。Pafm搜索营养障碍基因氨基端CH1区命中指数由108下降至36.5,期望值由2.3e-29上升至8.1e-08。3号外显子缺失使营养障碍基因肌动蛋白结合区域CH1区的螺旋区C缺失。结论3号外显子缺失后,营养障碍基因肌动蛋白结合区域的CH1区空间构像稳定性下降,且不能形成与肌动蛋白结合的结合面,从而影响营养障碍基因与肌动蛋白结合。信息生物学方法可为DMD的发病机制研究提供新的途径。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 aRer exon 3 deletion using SWISS-MODEL server. The motifs and structural domains of dystrophin aRer 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 fi＇om 2.3e-9 to 8.1e-8. The deletion also resulted in the absence of the spiral region C from the CHl domain. Conclusion Exon 3 deletion in the dystrophin-coding sequence decreases the stability of CHl 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.

关 键 词：营养障碍基因蛋白 蛋白空间结构 发病机制 

分 类 号：R346[医药卫生—基础医学]