Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Ave, Boston, Massachusetts, 02115.
J Comput Chem. 2020 Feb 15;41(5):402-414. doi: 10.1002/jcc.26060. Epub 2019 Sep 4.
The Ras GTPase superfamily of proteins coordinates a diverse set of cellular outcomes, including cell morphology, vesicle transport, and cell proliferation. Primary amino acid sequence analysis has identified Specificity determinant positions (SDPs) that drive diversified functions specific to the Ras, Rho, Rab, and Arf subfamilies (Rojas et al. 2012, J Cell Biol 196:189-201). The inclusion of water molecules in structural and functional adaptation is likely to be a major response to the selection pressures that drive evolution, yet hydration patterns are not included in phylogenetic analysis. This article shows that conserved crystallographic water molecules coevolved with SDP residues in the differentiation of proteins within the Ras superfamily of small GTPases. The patterns of water conservation between protein subfamilies parallel those of sequence-based evolutionary trees. Thus, hydration patterns have the potential to help elucidate functional significance in the evolution of amino acid residues observed in phylogenetic analysis of homologous proteins. © 2019 Wiley Periodicals, Inc.
Ras GTPase 蛋白超家族协调了多种细胞结果，包括细胞形态、囊泡运输和细胞增殖。初级氨基酸序列分析确定了特异性决定位置（SDP），这些位置驱动了 Ras、Rho、Rab 和 Arf 亚家族特有的多样化功能（Rojas 等人，2012 年，J Cell Biol 196:189-201）。水在结构和功能适应中的包含很可能是对推动进化的选择压力的主要反应，但水合模式并未包含在系统发育分析中。本文表明，在 Ras 小 GTP 酶超家族中小蛋白的分化中，保守的结晶水分子与 SDP 残基共同进化。蛋白亚家族之间的保水模式与基于序列的进化树模式平行。因此，水合模式有可能有助于阐明在同源蛋白的系统发育分析中观察到的氨基酸残基进化中的功能意义。© 2019 Wiley Periodicals, Inc.
