Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Divergent evolution of protein conformational dynamics in dihydrofolate reductase.
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DOI:
10.1038/nsmb.2676
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发表时间:
2013-11
影响因子:
16.8
通讯作者:
Wright, Peter E.
Wright, Peter E.
中科院分区:
生物学1区
文献类型:
--
作者:
Bhabha, Gira;Ekiert, Damian C.;Jennewein, Madeleine;Zmasek, Christian M.;Tuttle, Lisa M.;Kroon, Gerard;Dyson, H. Jane;Godzik, Adam;Wilson, Ian A.;Wright, Peter E.

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分子进化是由突变驱动的,突变可能会影响生物体的适应性,然后受到自然选择或遗传漂变的影响。蛋白质一级序列和三级结构的分析已经对蛋白质功能的进化产生了有价值的见解,但对活性所必需的功能机制、蛋白质动力学和构象可塑性的进化知之甚少。我们的特点是原子水平的运动跨越不同成员的二氢叶酸还原酶(DHFR)家庭。尽管结构相似,E.大肠杆菌和人DHFR使用不同的动力学机制来执行相同的功能,并且人DHFR不能补充DHFR缺陷的大肠杆菌。大肠杆菌细胞。识别的主要序列决定因素的灵活性,在DHFR从几个物种,使我们能够提出一个可能的情况下,功能重要的DHFR动态的演变,以下的模式,是由细胞环境调整的分歧演变。
Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, E. coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics, following a pattern of divergent evolution that is tuned by the cellular environment.
DOI: 10.1126/science.1198542
发表时间: 2011-04-08
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Bhabha G;Lee J;Ekiert DC;Gam J;Wilson IA;Dyson HJ;Benkovic SJ;Wright PE
通讯作者: Wright PE
DOI: 10.1107/s0907444904019158
发表时间: 2004-12-01
影响因子: 2.2
作者:
Emsley, P;Cowtan, K
通讯作者: Cowtan, K
DOI: 10.1089/106652702761034136
发表时间: 2002-01-01
影响因子: 1.7
作者:
Desper, R;Gascuel, O
通讯作者: Gascuel, O
DOI: 10.1126/science.1130258
发表时间: 2006-09-15
期刊: SCIENCE
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