UCD Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Republic of Ireland.
Proteins. 2011 May;79(5):1635-48. doi: 10.1002/prot.22990. Epub 2011 Mar 8.
Although important shifts in the isoelectric point of prokaryotic proteins, mainly due to adaptation to environmental pH, have been widely reported, such studies have not covered mammalian proteins, where pH changes may relate to changes in subcellular or tissue compartmentalization. We explored the isoelectric point of the proteome of 13 mammalian species. We detected proteins that have shifted their pI the most among 13 mammalian species, and investigated if these differences reflect adaptations of the orthologous proteins to different conditions. We find that proteins exhibiting a high isoelectric point change are enriched in certain GO terms, including immune defense, and mitochondrial proteins. We show that the shift in pI between orthologous proteins is not strongly associated with the overall rate of protein evolution, nor with protein length. Our results reveal that insertions/deletions are the main reason behind the shift of pI. However, for some proteins we find evidence of selection shifting the pI of the protein through amino acid replacement. Finally, we argue that shifts in pI might relate to the gain of additional activities, such as new interacting partners, in one ortholog as opposed to the other, and may potentially relate to functional differences between mammals.
尽管已有研究广泛报道原核生物蛋白质等电点的重要变化主要归因于对环境 pH 值的适应，但此类研究尚未涉及哺乳动物蛋白质，哺乳动物蛋白质的 pH 值变化可能与亚细胞或组织区室化的变化有关。我们探索了 13 种哺乳动物物种的蛋白质组等电点。我们检测了在 13 种哺乳动物物种中等电点变化最大的蛋白质，并研究了这些差异是否反映了同源蛋白质对不同条件的适应。我们发现，表现出高等电点变化的蛋白质在某些 GO 术语中富集，包括免疫防御和线粒体蛋白质。我们表明，同源蛋白质之间 pI 的变化与蛋白质进化的总体速率或蛋白质长度没有很强的关联。我们的研究结果表明，插入/缺失是 pI 变化的主要原因。然而，对于某些蛋白质，我们发现证据表明选择通过氨基酸替换来改变蛋白质的 pI。最后，我们认为 pI 的变化可能与一个同源物获得额外的活性（例如新的相互作用伙伴）有关，而不是另一个同源物，并且可能与哺乳动物之间的功能差异有关。
