本文選題：BK通道 + 同源建模��； 參考：《華中科技大學(xué)》2011年碩士論文

【摘要】：大電導(dǎo)鈣激活鉀離子(BK)通道是一類同時(shí)受控于膜電壓和胞內(nèi)鈣離子的特殊的鉀離子通道,它在很多重要的生理過程中有著非常重要的作用,如耳毛細(xì)胞的頻率調(diào)節(jié)和激素分泌、神經(jīng)遞質(zhì)的釋放、心率和血管的抗逆性等。因此,對(duì)BK通道結(jié)構(gòu)及調(diào)控機(jī)理的研究對(duì)于神經(jīng)科學(xué)以及心血管疾病的研究都有著重要意義。 本論文利用BLAST對(duì)mslo1序列在蛋白質(zhì)結(jié)構(gòu)數(shù)據(jù)庫(kù)(PDB庫(kù))中進(jìn)行同源性搜索:利用MODELLER對(duì)搜索結(jié)果中得分較高的跨膜區(qū)S1-S6進(jìn)行同源建模,模板為Kv1.2通道的晶體結(jié)構(gòu)(PDB ID,2R9R);而得分較低的N端部分則采用ROSETTA進(jìn)行從頭計(jì)算得到;RCK結(jié)構(gòu)直接利用hslo1的晶體結(jié)構(gòu)(PDB ID,3NAF)。參考MthK通道以及電鏡實(shí)驗(yàn)結(jié)果組裝BK通道全結(jié)構(gòu)。 通過與KCNQ1通道的序列比對(duì),對(duì)比新得到的BK通道模型,發(fā)現(xiàn)S1上的兩個(gè)殘基(Y130、F131)和相鄰亞基的S5上的A250、以及孔區(qū)α螺旋上的W275之間形成了一個(gè)相互作用區(qū)域,這個(gè)作用區(qū)域可能在通道門控調(diào)控中起著重要的作用。本論文同時(shí)還利用ROSETTA對(duì)dslo1的S0-S1 linker進(jìn)行了建模,通過對(duì)mslo1和dslo1的linker區(qū)進(jìn)行比較,發(fā)現(xiàn)mslo1的S0-S1 linker的結(jié)構(gòu)中,存在著兩個(gè)α螺旋結(jié)構(gòu),而dslo1相應(yīng)的肽鏈片段則為無規(guī)則卷曲,而這段無規(guī)則卷曲可能正好破壞了β2與通道的作用通路。
[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 偽 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 偽 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.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R341

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本文編號(hào)：1957977