Chemes Lucía Beatriz, de Prat-Gay Gonzalo, Sánchez Ignacio Enrique
Protein Structure-Function and Engineering Laboratory, Fundación Instituto Leloir and IIBBA-CONICET, Av. Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
Protein Structure-Function and Engineering Laboratory, Fundación Instituto Leloir and IIBBA-CONICET, Av. Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
Curr Opin Struct Biol. 2015 Jun;32:91-101. doi: 10.1016/j.sbi.2015.03.004. Epub 2015 Apr 2.
Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment.
病原体线性基序模拟物是高度可进化的元件，有助于宿主蛋白质相互作用网络的重新布线。宿主线性基序和病原体模拟物在序列上存在差异，导致所产生的蛋白质-蛋白质相互作用在热力学和结构上存在差异。此外，模拟物的功能输出取决于病原体蛋白质的基序和结构域组成。通过测量进化速率、量化正选择和负选择以及对线性基序自然史进行系统发育重建，可以理解由线性基序介导的调控进化。线性基序模拟物的趋同进化在病毒、原核生物和真核生物病原体的不相关蛋白质中广泛存在，也可以在单个蛋白质系统发育中发生。感染的统计学、生物化学和实验室模型将病原体线性基序与诸如嗜性、毒力和致癌性等表型特征联系起来。体外进化实验和天然序列分析表明，线性基序组成的变化是病原体适应不断变化环境的基础。
