The Experts below are selected from a list of 9684 Experts worldwide ranked by ideXlab platform
Yoshinori Ohsumi - One of the best experts on this subject based on the ideXlab platform.
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atg12 atg5 conjugate enhances e2 activity of atg3 by rearranging its catalytic site
Nature Structural & Molecular Biology, 2013Co-Authors: Machiko Sakohnakatogawa, Eri Asai, Kazuaki Matoba, Junko Ishii, Nobuo N. Noda, Fuyuhiko Inagaki, Hiromi Kirisako, Hitoshi Nakatogawa, Yoshinori OhsumiAbstract:In the yeast autophagy system, the Atg12–Atg5 conjugate acts as an E3 to promote the E2 activity of Atg3, which conjugates Atg8 to phosphatidylethanolamine. Now structural and biochemical analyses reveal that Atg12–Atg5 induces a rearrangement in the catalytic center of Atg3, which employs a Threonine Residue in addition to the active cysteine to catalyze the conjugation reaction.
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atg12 atg5 conjugate enhances e2 activity of atg3 by rearranging its catalytic site
Nature Structural & Molecular Biology, 2013Co-Authors: Machiko Sakohnakatogawa, Eri Asai, Kazuaki Matoba, Junko Ishii, Nobuo N. Noda, Fuyuhiko Inagaki, Hiromi Kirisako, Hitoshi Nakatogawa, Yoshinori OhsumiAbstract:In the yeast autophagy system, the Atg12–Atg5 conjugate acts as an E3 to promote the E2 activity of Atg3, which conjugates Atg8 to phosphatidylethanolamine. Now structural and biochemical analyses reveal that Atg12–Atg5 induces a rearrangement in the catalytic center of Atg3, which employs a Threonine Residue in addition to the active cysteine to catalyze the conjugation reaction.
Xuhui Huang - One of the best experts on this subject based on the ideXlab platform.
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bridge helix bending promotes rna polymerase ii backtracking through a critical and conserved Threonine Residue
Nature Communications, 2016Co-Authors: Lintai Da, Fatima Pardoavila, Liang Xu, Danieladriano Silva, Lu Zhang, D Wang, Xuhui HuangAbstract:The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH Residue T831 as a sensing probe for the 3′-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3′-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation. RNA Polymerase II can detect and cleave mis-incorporated nucleotides by a proofreading mechanism that requires backtracking of the enzyme. Here the authors show that Pol II backtracking occurs in a stepwise mode that involves two intermediate states where the fraying of the terminal RNA nucleotide is a prerequisite.
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bridge helix bending promotes rna polymerase ii backtracking through a critical and conserved Threonine Residue
Nature Communications, 2016Co-Authors: Fatima Pardoavila, Danieladriano Silva, Lu Zhang, D Wang, Xin Gao, Xuhui HuangAbstract:The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH Residue T831 as a sensing probe for the 3'-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3'-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation.
Danieladriano Silva - One of the best experts on this subject based on the ideXlab platform.
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bridge helix bending promotes rna polymerase ii backtracking through a critical and conserved Threonine Residue
Nature Communications, 2016Co-Authors: Lintai Da, Fatima Pardoavila, Liang Xu, Danieladriano Silva, Lu Zhang, D Wang, Xuhui HuangAbstract:The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH Residue T831 as a sensing probe for the 3′-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3′-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation. RNA Polymerase II can detect and cleave mis-incorporated nucleotides by a proofreading mechanism that requires backtracking of the enzyme. Here the authors show that Pol II backtracking occurs in a stepwise mode that involves two intermediate states where the fraying of the terminal RNA nucleotide is a prerequisite.
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bridge helix bending promotes rna polymerase ii backtracking through a critical and conserved Threonine Residue
Nature Communications, 2016Co-Authors: Fatima Pardoavila, Danieladriano Silva, Lu Zhang, D Wang, Xin Gao, Xuhui HuangAbstract:The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH Residue T831 as a sensing probe for the 3'-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3'-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation.
Joseph W. Lynch - One of the best experts on this subject based on the ideXlab platform.
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comparative surface accessibility of a pore lining Threonine Residue t6 in the glycine and gaba a receptors
Biophysical Journal, 2003Co-Authors: Joseph W. Lynch, Qiang Shan, Justine L HaddrillAbstract:The substituted cysteine accessibility method was used to probe the surface exposure of a pore-lining Threonine Residue (T6’) common to both the glycine receptor (GlyR) and GABAA receptor (GABAAR) chloride channels. This Residue lies close to the channel activation gate, the ionic selectivity filter and the main pore blocker binding site. Recent studies have suggested that the GlyRs and GABAARs have divergent open state pore structures at the 6’ position. When both the human a1T6’C homomeric GlyR and the rat a1T6’Cb1T6’C heteromeric GABAAR were expressed in HEK293 cells, their 6’ Residue surface accessibilities differed significantly in the closed state. However, when a soluble cysteine-modifying compound was applied in the presence of saturating agonist concentrations, both receptors were locked into the open state. This action was not induced by oxidising agents in either receptor. These results provide evidence for a conserved pore opening mechanism in anion-selective members of the ligand-gated ion channel family. The results also indicate that the GABAAR pore structure at the 6’ level may vary between different expression systems.
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comparative surface accessibility of a pore lining Threonine Residue t6 in the glycine and gabaa receptors
Journal of Biological Chemistry, 2002Co-Authors: Qiang Shan, Justine L Haddrill, Joseph W. LynchAbstract:The substituted cysteine accessibility method was used to probe the surface exposure of a pore-lining Threonine Residue (T6') common to both the glycine receptor (GlyR) and gamma-aminobutyric acid, type A receptor (GABA(A)R) chloride channels. This Residue lies close to the channel activation gate, the ionic selectivity filter, and the main pore blocker binding site. Despite their high amino acid sequence homologies and common role in conducting chloride ions, recent studies have suggested that the GlyRs and GABA(A)Rs have divergent open state pore structures at the 6' position. When both the human alpha1(T6'C) homomeric GlyR and the rat alpha1(T6'C)beta1(T6'C) heteromeric GABA(A)R were expressed in human embryonic kidney 293 cells, their 6' Residue surface accessibilities differed significantly in the closed state. However, when a soluble cysteine-modifying compound was applied in the presence of saturating agonist concentrations, both receptors were locked into the open state. This action was not induced by oxidizing agents in either receptor. These results provide evidence for a conserved pore opening mechanism in anion-selective members of the ligand-gated ion channel family. The results also indicate that the GABA(A)R pore structure at the 6' level may vary between different expression systems.
Machiko Sakohnakatogawa - One of the best experts on this subject based on the ideXlab platform.
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atg12 atg5 conjugate enhances e2 activity of atg3 by rearranging its catalytic site
Nature Structural & Molecular Biology, 2013Co-Authors: Machiko Sakohnakatogawa, Eri Asai, Kazuaki Matoba, Junko Ishii, Nobuo N. Noda, Fuyuhiko Inagaki, Hiromi Kirisako, Hitoshi Nakatogawa, Yoshinori OhsumiAbstract:In the yeast autophagy system, the Atg12–Atg5 conjugate acts as an E3 to promote the E2 activity of Atg3, which conjugates Atg8 to phosphatidylethanolamine. Now structural and biochemical analyses reveal that Atg12–Atg5 induces a rearrangement in the catalytic center of Atg3, which employs a Threonine Residue in addition to the active cysteine to catalyze the conjugation reaction.
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atg12 atg5 conjugate enhances e2 activity of atg3 by rearranging its catalytic site
Nature Structural & Molecular Biology, 2013Co-Authors: Machiko Sakohnakatogawa, Eri Asai, Kazuaki Matoba, Junko Ishii, Nobuo N. Noda, Fuyuhiko Inagaki, Hiromi Kirisako, Hitoshi Nakatogawa, Yoshinori OhsumiAbstract:In the yeast autophagy system, the Atg12–Atg5 conjugate acts as an E3 to promote the E2 activity of Atg3, which conjugates Atg8 to phosphatidylethanolamine. Now structural and biochemical analyses reveal that Atg12–Atg5 induces a rearrangement in the catalytic center of Atg3, which employs a Threonine Residue in addition to the active cysteine to catalyze the conjugation reaction.