論蛋白質間接觸面的結構堆疊與序列上胺基酸保留性之關係

Abstract

蛋白質藉由與其他蛋白質作用而實施它們的生物功能。因此,蛋白質間接 觸面的知識對於了解分子機制是有價值的。近來,我們觀察到蛋白質們的結構堆疊程度檔案(structural packing profile)和序列上胺基酸保留程度檔案 (conservation profile)有良好的相關性,其中蛋白質們的結構堆疊程度檔案是僅 在單個蛋白質結構中運用加權接觸數模型 (weighted contact number model)所計 算出。然而,有些蛋白質的這兩種檔案相關性極低。為了更加了解蛋白質間接 觸面的特性,我們探討 328 個酵素複合體中的 344 個不同源次單元們蛋白質間 接觸面的結構堆疊程度與序列上胺基酸保留程度之關係。這些次單位們組成三 個資料組,分別是 Set I、Set A 和 Set B。Set A 中,酵素複合體的催化位是在接 觸面而且由來自多個次單元們的殘基們所組成,而 Set B 中,酵素複合體的催 化位是不在接觸面而且由來自單個次單元們的殘基們所組成。我們發現三個資 料組的接觸面殘基們傾向擁有高加權接觸數分數 (等同於不緊密堆疊)。然而, Set B 的接觸面殘基們傾向擁有高胺基酸保留性分數(等同於胺基酸保留性低), 此種傾向不同於其他資料組們的傾向。這也許是因為在酵素維持功能的情況下 ,Set B 中的複合體們比其他資料組們中的複合體們在演化過程中受到較微弱的 功能上與結構上的限制。令人訝異的是,研究結果顯示三個資料組中的接觸面 殘基們擁有不同於非接觸面殘基們的加權接觸數分數與胺基酸保留性分數之間 的分數差之分佈,而且接觸面殘基們的加權接觸數分數傾向高於它們相對的胺基酸保留性分數。此外,利用殘基的加權接觸數分數與胺基酸保留性分數之間的分數差去預測這些蛋白質間接觸面獲得極高的敏感度。此研究提供接觸面殘基結構堆疊程度與序列上胺基酸保留程度的特性,並且闡述蛋白質間接觸面的結構堆疊程度與序列上胺基酸保留程度之關係。

Proteins interact with other proteins to perform their biological functions. Thus, the knowledge of protein-protein interfaces is valuable in understanding molecular mechanisms. Recently, we have observed that structural packing profiles of proteins have moderate correlations with their corresponding conservation profiles. However, some proteins were found to have low correlations between these two profiles, where structural packing profiles of the proteins were computed using a weighted contact number (WCN) model with the structures of single proteins. To better understand the characteristics in protein-protein interfaces, we explored the relationship between structural packing and residue conservation in protein-protein interfaces from 344 non-homologous subunits of 328 enzymes complexes. These subunits compose three datasets: Set I, Set A, and Set B. In Set A, catalytic sites of complexes are in the interfaces and consist of residues from multiple subunits; in Set B, catalytic sites of complexes are not in the interfaces and consist of residues from single subunits. We found that interface residues in three datasets tend to have high WCN scores (i.e., low structural packing). However, interface residues of Set B tend to have high conservation scores (i.e., lowly conserved). The tendency is different from those of the other datasets. This could be that complexes of Set B have weaker functional and structural constraints on their evolutionary processes than those of the other datasets in the condition that the enzymatic functions of the complexes are maintained. Surprisingly, the results show that the interface residues have distinct distributions of differences between the WCN scores and the conservation scores from the non-interface residues. Also, the WCN scores of the interface residues tend to be higher than their corresponding conservation scores. Furthermore, using a difference between a WCN score and a conservation score of a residue to detect the protein-protein interfaces, noteworthy sensitivity was obtained. This study provides interface properties in structural packing and residue conservation and elucidates the relationship between the structural packing and the residue conservation in interfaces of individual subunits.