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Unique 5′-P recognition and basis for dG:dGTP misincorporation of ASFV DNA polymerase X
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نویسنده
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chen y. ,zhang j. ,liu h. ,gao y. ,li x. ,zheng l. ,cui r. ,yao q. ,rong l. ,li j. ,huang z. ,ma j. ,gan j.
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منبع
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plos biology - 2017 - دوره : 15 - شماره : 2
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چکیده
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African swine fever virus (asfv) can cause highly lethal disease in pigs and is becoming a global threat. asfv dna polymerase x (asfvpolx) is the most distinctive dna polymerase identified to date; it lacks two dna-binding domains (the thumb domain and 8-kd domain) conserved in the homologous proteins. asfvpolx catalyzes the gap-filling reaction during the dna repair process of the asfv virus genome; it is highly error prone and plays an important role during the strategic mutagenesis of the viral genome. the structural basis underlying the natural substrate binding and the most frequent dg:dgtp misincorporation of asfvpolx remain poorly understood. here,we report eight asfvpolx complex structures; our structures demonstrate that asfvpolx has one unique 5′-phosphate (5′-p) binding pocket,which can favor the productive catalytic complex assembly and enhance the dgtp misincorporation efficiency. in combination with mutagenesis and in vitro catalytic assays,our study also reveals the functional roles of the platform his115-arg127 and the hydrophobic residues val120 and leu123 in dg:dgtp misincorporation and can provide information for rational drug design to help combat asfv in the future. © 2017 chen et al.
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آدرس
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state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of physiology and biophysics,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of physiology and biophysics,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of physiology and biophysics,school of life sciences,fudan university,shanghai,china,state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of biochemistry,institute of plant biology,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of physiology and biophysics,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of biochemistry,institute of plant biology,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of biochemistry,institute of plant biology,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of biochemistry,institute of plant biology,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of biochemistry,institute of plant biology,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of biochemistry,institute of plant biology,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of physiology and biophysics,school of life sciences,fudan university,shanghai, China, department of chemistry,georgia state university,atlanta,ga,united states,college of life sciences,sichuan university,chengdu, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of biochemistry,institute of plant biology,school of life sciences,fudan university,shanghai, China, state key laboratory of genetic engineering,collaborative innovation center of genetics and development,department of physiology and biophysics,school of life sciences,fudan university,shanghai, China
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Authors
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