Were Ancestral Proteins Less Specific?
Were Ancestral Proteins Less Specific?
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DOI：
10.1093/molbev/msab019
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发表时间：
2021-05-19
影响因子：
10.7
通讯作者：
Harms MJ
中科院分区：
文献类型：
--
作者：
Wheeler LC;Harms MJ
有些人假设祖先蛋白质的特异性平均低于其后代。如果这是真的，这将提供一个沿着组织蛋白质进化的通用轴，并表明重建的祖先蛋白质可能是蛋白质工程的独特强大工具。祖先序列重建研究是用来支持这一假设的证据之一。在此之前，我们进行了这样的研究，研究了旁系同源物S100 A5和S100 A6的肽结合特异性的演变。现代蛋白质比它们最后的共同祖先（ancA 5/A6）更具有特异性，因为每个蛋白质结合ancA 5/A6结合的肽的子集。在这项研究中，我们重新审视了这一转变，使用定量噬菌体展示来测量30，533个随机肽与人S100 A5，S100 A6和ancA 5/A6的相互作用。这个不带偏见的屏幕揭示了一个不同的画面。虽然S100 A5和S100 A6确实与ancA 5/A6识别的肽的子集结合，但它们也获得了ancA 5/A6识别的肽组之外的新肽配偶体。我们以前的工作表明，当针对生物靶标测量时，ancA 5/A6的特异性低于其后代;我们的新工作表明，当针对随机的一组肽靶标测量时，ancA 5/A6与现代蛋白质具有相似的特异性。这表明，改变的生物特异性并不一定表明改变的内在特异性，并使用祖先重建研究与生物靶点作为一种手段来推断特异性的全球进化趋势的警示。
Some have hypothesized that ancestral proteins were, on average, less specific than their descendants. If true, this would provide a universal axis along which to organize protein evolution and suggests that reconstructed ancestral proteins may be uniquely powerful tools for protein engineering. Ancestral sequence reconstruction studies are one line of evidence used to support this hypothesis. Previously, we performed such a study, investigating the evolution of peptide-binding specificity for the paralogs S100A5 and S100A6. The modern proteins appeared more specific than their last common ancestor (ancA5/A6), as each paralog bound a subset of the peptides bound by ancA5/A6. In this study, we revisit this transition, using quantitative phage display to measure the interactions of 30,533 random peptides with human S100A5, S100A6, and ancA5/A6. This unbiased screen reveals a different picture. While S100A5 and S100A6 do indeed bind to a subset of the peptides recognized by ancA5/A6, they also acquired new peptide partners outside of the set recognized by ancA5/A6. Our previous work showed that ancA5/A6 had lower specificity than its descendants when measured against biological targets; our new work shows that ancA5/A6 has similar specificity to the modern proteins when measured against a random set of peptide targets. This demonstrates that altered biological specificity does not necessarily indicate altered intrinsic specificity, and sounds a cautionary note for using ancestral reconstruction studies with biological targets as a means to infer global evolutionary trends in specificity.
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影响因子：
4.6
作者：
Alhindi T;Zhang Z;Ruelens P;Coenen H;Degroote H;Iraci N;Geuten K
通讯作者：
Geuten K
影响因子：
48
作者：
Fowler, Douglas M.;Fields, Stanley
通讯作者：
Fields, Stanley
影响因子：
15
作者：
Devamani T;Rauwerdink AM;Lunzer M;Jones BJ;Mooney JL;Tan MA;Zhang ZJ;Xu JH;Dean AM;Kazlauskas RJ
通讯作者：
Kazlauskas RJ
DOI：
10.1126/science.1233465
发表时间：
2013-05-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Reinke AW;Baek J;Ashenberg O;Keating AE
通讯作者：
Keating AE
影响因子：
10.7
作者：
Eick, Geeta N.;Bridgham, Jamie T.;Thornton, Joseph W.
通讯作者：
Thornton, Joseph W.