CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study t...CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCRI-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCRI-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCRI-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation.展开更多
Dear Editor, Telomeres are specific protein-DNA complexes that pro- tect the ends of eukaryotic chromosomes from fusion and degradation and are maintained by a specialized mecha- nism exerted by telomerase and telome...Dear Editor, Telomeres are specific protein-DNA complexes that pro- tect the ends of eukaryotic chromosomes from fusion and degradation and are maintained by a specialized mecha- nism exerted by telomerase and telomere-binding proteins. Mammalian telomeres contain TTAGGG and are associated with a six-protein （e.g. TRF1, TRF2, TIN2, RAP1, POT1, and TPP1） complex called shelterin （de Lange, 2005）, which was involved in telomere homeostasis. Similarly to mammalian telomeres, telomeres in most plants are maintained by tel- omerase and telomere-associated proteins （e.g. AtTBP1, AtTRP1, AtTRB1, POT1, POT2, KU70, and KU80） and consist of tandem arrays of TTTAGGG. Among telomere-associated proteins in Arabidopsis thaliana, AtTRB proteins belong to the SMH （Single-Myb-Histone）-Iike family, in which proteins are composed of an N-terminal Myb domain, a central his- tone Hl-like globular domain, and a C-terminal coiled-coil region.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11575021,U1530401,and U1430237)the National Research Foundation of Korea(Grant Nos.NRF-2017R1A2B2008483 and NRF-2016R1A6A3A04010213)
文摘CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCRI-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCRI-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCRI-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation.
文摘Dear Editor, Telomeres are specific protein-DNA complexes that pro- tect the ends of eukaryotic chromosomes from fusion and degradation and are maintained by a specialized mecha- nism exerted by telomerase and telomere-binding proteins. Mammalian telomeres contain TTAGGG and are associated with a six-protein （e.g. TRF1, TRF2, TIN2, RAP1, POT1, and TPP1） complex called shelterin （de Lange, 2005）, which was involved in telomere homeostasis. Similarly to mammalian telomeres, telomeres in most plants are maintained by tel- omerase and telomere-associated proteins （e.g. AtTBP1, AtTRP1, AtTRB1, POT1, POT2, KU70, and KU80） and consist of tandem arrays of TTTAGGG. Among telomere-associated proteins in Arabidopsis thaliana, AtTRB proteins belong to the SMH （Single-Myb-Histone）-Iike family, in which proteins are composed of an N-terminal Myb domain, a central his- tone Hl-like globular domain, and a C-terminal coiled-coil region.
