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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Determining the basis of channel-tetramerization specificity by x-ray crystallography and a sequence-comparison algorithm: Family values (FamVal).
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Determining the basis of channel-tetramerization specificity by x-ray crystallography and a sequence-comparison algorithm: Family values (FamVal).

机译:通过X射线晶体学和序列比较算法确定通道四聚体特异性的基础:家族值(FamVal)。

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摘要

We have developed a semiempirical algorithm called Family Values (FamVal), which identifies residues that encode functional specificity in a protein sequence. Given a multiple sequence alignment (MSA) grouped into functionally distinct subfamilies, FamVal calculates a specificity score for each subfamily at every amino acid position of an MSA. This algorithm was used to predict specificity-encoding positions within the tetramerization assembly (T1) domain of voltage-gated potassium (Kv) channel subfamilies Kv3 and Kv4. The importance of one such position (Arg to Ala at MSA position 93) was confirmed by in vitro pull-down assays. The structural basis of this assembly discrimination was elucidated by determining the crystal structure of the Kv4 T1 domain and comparing it to the Kv3 T1 domain.
机译:我们已经开发了一种称为“家族值”(FamVal)的半经验算法,该算法可识别编码蛋白质序列中功能特异性的残基。给定功能上不同的亚家族分组的多序列比对(MSA),FamVal计算MSA的每个氨基酸位置上每个亚家族的特异性得分。此算法用于预测电压门控钾(Kv)通道亚家族Kv3​​和Kv4的四聚体装配(T1)域内的特异性编码位置。通过体外下拉测定法证实了这样一个位置的重要性(在MSA 93位置的Arg相对于Ala)。通过确定Kv4 T1域的晶体结构并将其与Kv3 T1域进行比较,阐明了这种装配区分的结构基础。

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