蛋白質精胺酸甲基轉移酶受質序列之探討

近幾年來許多研究已經發現在histone及其他的蛋白質上的甲基化會參與基因轉錄的調控。蛋白質甲基化為共價性轉譯後修飾由蛋白質精胺酸甲基轉移酶(PRMT)催化完成，在細胞生長、基因表現和訊息傳導調控機制中，扮演很重要的地位。目前已發現多種PRMT受質既包括组蛋白也包括大量的非组蛋白，也知道部分PRMT偏好的結構形式，但對於各類型的PRMT是否有特定專一性或識別特定排序的胺基酸了解甚少。本研究中，我們將利用生物資訊的方法探討序列上蛋白質精胺酸甲基化的位置與周遭結構及各種類PRMT之間的關係。同時我們利用軟體對這些蛋白質序列進行轉譯後修飾的預測，例如磷酸化位點等，再進一步分析這些轉譯後修飾與甲基化之間的關係。根據前人的研究，我們收集了1000多個蛋白精胺酸甲基化的位點，來自於807條人類蛋白質序列。我們利用演化分析軟體BLAST-Based Relative Distance (BBRD)對這些胜肽序列行進行分群，利用這些已分群的胜肽序列找尋有無精胺酸甲基化特定的序列型態(pattern)出現。經過篩選最後選定的21個子群裡，對每一子群使用PRATT軟體找尋conserved patterns，其中有15組能歸納出特定的序列型態，將這些patterns與前人文獻報告已知的PRMT受質，精胺酸甲基化位點序列是否有相符合。磷酸化研究結果顯示將近6成的磷酸化位點在距離甲基化位點10個胺基酸以內，這結果表示存在磷酸化與甲基化相互影響的可能性。PRMT受質之序列專一性分析雖然並沒有明確的指示出哪一pattern為哪一型PRMT的識別的序列，但也表明了這種方法來研究的可能性。

關鍵字

精胺酸；甲基化；精氨酸甲基轉移酶

並列摘要

In recent years, many studies have found that the methylations on histone and other proteins are involved in the regulation of gene transcription. Protein methylation is a covalent post-translational modification. It plays a very important role in cell growth, regulation of gene expression and signal conduction. It has been found a variety of PRMT substrate including histone and non-histone protein as well as preferred structure of PRMT. However, the particular structure of PRMT and specific target amino acid sequences have not been studied extensively. The objectives of the present study were to use bioinformatics method to explore the sequence position of protein arginine methylation, surrounding structure and relationship between the various class of PRMT. Meanwhile, we used the software to predict post-translational modification site such as phosphorylation sites. Finally, we will analyze the possible interactions among those post-translational modifications. According to the previous studies, we collected more than 1000 protein arginine methylation sites derived from 807 protein sequences. These proteins were subjected to a BLAST-Based Relative Distance (BBRD) tool to evaluate the evolutionary relationship among those proteins, then to identify the consensus arginine methylation target sequences for the sub-tree. After screening out this sequence to generate 21 subgroups which using PRATT software to search for patterns conserved in each subgroup. It produced 15 group of conserved sequence. Furthermore, we organize many type of substrate protein and compare with PRATT result. These patterns compare with previous studies of PRMT substrate whether arginine methylation sequence is consistent. The results showed that nearly 60 percent of the phosphorylation sites are within 10 residues of the methylation sites, indicating the possibility that phosphorylation and methylation may affect each other. The analysis of substrate sequence specificity remain poorly understood that PRMT recognize which pattern of sequence, but this approach shows the possibility of research.

並列關鍵字

arginine ； methylation ； arginine methyltransferases

參考文獻

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蛋白質精胺酸甲基轉移酶受質序列之探討

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