BK通道三维结构模拟研究

发布时间：2018-05-31 02:36

本文选题：BK通道 + 同源建模　；参考：《华中科技大学》2011年硕士论文

【摘要】：大电导钙激活钾离子(BK)通道是一类同时受控于膜电压和胞内钙离子的特殊的钾离子通道,它在很多重要的生理过程中有着非常重要的作用,如耳毛细胞的频率调节和激素分泌、神经递质的释放、心率和血管的抗逆性等。因此,对BK通道结构及调控机理的研究对于神经科学以及心血管疾病的研究都有着重要意义。本论文利用BLAST对mslo1序列在蛋白质结构数据库(PDB库)中进行同源性搜索:利用MODELLER对搜索结果中得分较高的跨膜区S1-S6进行同源建模,模板为Kv1.2通道的晶体结构(PDB ID,2R9R);而得分较低的N端部分则采用ROSETTA进行从头计算得到;RCK结构直接利用hslo1的晶体结构(PDB ID,3NAF)。参考MthK通道以及电镜实验结果组装BK通道全结构。通过与KCNQ1通道的序列比对,对比新得到的BK通道模型,发现S1上的两个残基(Y130、F131)和相邻亚基的S5上的A250、以及孔区α螺旋上的W275之间形成了一个相互作用区域,这个作用区域可能在通道门控调控中起着重要的作用。本论文同时还利用ROSETTA对dslo1的S0-S1 linker进行了建模,通过对mslo1和dslo1的linker区进行比较,发现mslo1的S0-S1 linker的结构中,存在着两个α螺旋结构,而dslo1相应的肽链片段则为无规则卷曲,而这段无规则卷曲可能正好破坏了β2与通道的作用通路。
[Abstract]:Large conductance calcium activated potassium ion (BK) channel is a special potassium channel controlled by both membrane voltage and intracellular calcium ion. It plays a very important role in many important physiological processes, such as frequency regulation and hormone secretion in ear hair cells. Neurotransmitter release, heart rate and vascular resistance, etc. Therefore, the study of BK channel structure and regulation mechanism is of great significance for neuroscience and cardiovascular disease. In this paper, BLAST was used to search the homology of mslo1 sequences in the protein structure database. MODELLER was used to model the high score S1-S6 in the cross-membrane region. The crystal structure of Kv1.2 channel is Kv1.2 channel, while the N terminal with lower score is calculated by ab initio calculation with ROSETTA. The crystal structure of hslo1 is directly used to make use of the crystal structure of hslo1. The whole structure of BK channel was assembled by MthK channel and electron microscope. By comparing the new BK channel model with the sequence alignment of the KCNQ1 channel, it was found that an interaction region was formed between the two residues on S1 and the A250 on the S5 of the adjacent subunit, and the W275 on the 伪 helix of the pore region. This area of action may play an important role in channel gated regulation. At the same time, the S0-S1 linker of dslo1 is modeled by ROSETTA. By comparing the linker region of mslo1 and dslo1, it is found that there are two 伪 helical structures in the S0-S1 linker of mslo1, and the corresponding peptide chain fragment of dslo1 is irregular crimp. And this irregular curl may just destroy the pathway of 尾 2 and channel.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R341

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