The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform
Christy F. Landes - One of the best experts on this subject based on the ideXlab platform.
-
Mechanistic Understanding of the Phosphorylation-Induced Conformational Rigidity at the AMPA Receptor C-terminal Domain
ACS omega, 2019Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Christy F. LandesAbstract:Phosphorylation at the intracellular C-terminal domain (CTD) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induces conformational rigidity. Such intracellular alterations to the AMPA receptor influence its functional responses, which are involved in multiple synaptic processes and neuronal signaling. The structure of the CTD still remains unresolved, which poses challenges toward providing a mechanism for the process of phosphorylation and deciphering the role of each phosphorylation step in causing the resultant conformational behavior. Herein, we utilize smFRET Spectroscopy to understand the mechanism of phosphorylation, with the help of strategic point mutations that mimic phosphorylation. Our results reveal that first, phosphorylation at three target sites (S818, S831, and T840) is necessary for the change in the secondary structure of the existing disordered native sequence. Also, the results suggest that the formation of the tertiary structure through electrostatic interac...
-
Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors
Journal of Physical Chemistry B, 2018Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Caitlin E. Nurik, Vasanthi Jayaraman, Christy F. LandesAbstract:The intracellular C-terminal domain (CTD) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor undergoes phosphorylation at specific locations during long-term potentiation. This modification enhances conductance through the AMPA receptor ion channel and thus potentially plays a crucial role in modulating receptor trafficking and signaling. However, because the CTD structure is largely unresolved, it is difficult to establish if phosphorylation induces conformational changes that might play a role in enhancing channel conductance. Herein, we utilize single-molecule Forster resonance energy transfer (smFRET) Spectroscopy to probe the conformational changes of a section of the AMPA receptor CTD, under the conditions of point-mutated phosphomimicry. Multiple analysis algorithms fail to identify stable conformational states within the smFRET distributions, consistent with a lack of well-defined secondary structure. Instead, our results show that phosphomimicry induces conformational rigidit...
-
Wavelet Shrinkage to Resolve Single Molecule FRET Structural Landscape of the Isolated Ligand Binding Domain of the AMPA Receptor
Biophysical Journal, 2011Co-Authors: Christy F. Landes, J. Nick Taylor, Anu Rambhadran, Vasanthi JayaramanAbstract:Single molecule fluorescence resonance energy transfer (smFRET) Spectroscopy has provided significant advances in our understanding of the relationship between structure and function in biological systems. Currently, simplifications must be made for experimental systems, data analysis, and theoretical modeling because biomolecules often exhibit mechanistic or conformational heterogeneity. For example, it is often necessary to treat biomolecular processes as transitions between two well-define states (e.g. folded vs. unfolded) despite clear experimental evidence or theoretical predictions to the contrary. The conformations explored by the agonist binding domain of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor represent such a system. The distribution of conformations in the raw data was so wide it was not possible to extract conformational details. By employing a model-free data analysis technique called wavelet shrinkage, it was determined that each protein form comprised multi-state, sequential equilibria. The results illustrate that the extent of activation is dependent not on a rigid closed cleft, but instead on the probability that a given subunit will occupy a closed cleft conformation, which in turn is determined by the range of states that the protein explores. Also, the results emphasize both the need for and the utility of advanced data processing techniques to quantify structure and dynamics in heterogeneous systems.
Sudeshna Chatterjee - One of the best experts on this subject based on the ideXlab platform.
-
Mechanistic Understanding of the Phosphorylation-Induced Conformational Rigidity at the AMPA Receptor C-terminal Domain
ACS omega, 2019Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Christy F. LandesAbstract:Phosphorylation at the intracellular C-terminal domain (CTD) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induces conformational rigidity. Such intracellular alterations to the AMPA receptor influence its functional responses, which are involved in multiple synaptic processes and neuronal signaling. The structure of the CTD still remains unresolved, which poses challenges toward providing a mechanism for the process of phosphorylation and deciphering the role of each phosphorylation step in causing the resultant conformational behavior. Herein, we utilize smFRET Spectroscopy to understand the mechanism of phosphorylation, with the help of strategic point mutations that mimic phosphorylation. Our results reveal that first, phosphorylation at three target sites (S818, S831, and T840) is necessary for the change in the secondary structure of the existing disordered native sequence. Also, the results suggest that the formation of the tertiary structure through electrostatic interac...
-
Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors
Journal of Physical Chemistry B, 2018Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Caitlin E. Nurik, Vasanthi Jayaraman, Christy F. LandesAbstract:The intracellular C-terminal domain (CTD) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor undergoes phosphorylation at specific locations during long-term potentiation. This modification enhances conductance through the AMPA receptor ion channel and thus potentially plays a crucial role in modulating receptor trafficking and signaling. However, because the CTD structure is largely unresolved, it is difficult to establish if phosphorylation induces conformational changes that might play a role in enhancing channel conductance. Herein, we utilize single-molecule Forster resonance energy transfer (smFRET) Spectroscopy to probe the conformational changes of a section of the AMPA receptor CTD, under the conditions of point-mutated phosphomimicry. Multiple analysis algorithms fail to identify stable conformational states within the smFRET distributions, consistent with a lack of well-defined secondary structure. Instead, our results show that phosphomimicry induces conformational rigidit...
Vasanthi Jayaraman - One of the best experts on this subject based on the ideXlab platform.
-
Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors
Journal of Physical Chemistry B, 2018Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Caitlin E. Nurik, Vasanthi Jayaraman, Christy F. LandesAbstract:The intracellular C-terminal domain (CTD) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor undergoes phosphorylation at specific locations during long-term potentiation. This modification enhances conductance through the AMPA receptor ion channel and thus potentially plays a crucial role in modulating receptor trafficking and signaling. However, because the CTD structure is largely unresolved, it is difficult to establish if phosphorylation induces conformational changes that might play a role in enhancing channel conductance. Herein, we utilize single-molecule Forster resonance energy transfer (smFRET) Spectroscopy to probe the conformational changes of a section of the AMPA receptor CTD, under the conditions of point-mutated phosphomimicry. Multiple analysis algorithms fail to identify stable conformational states within the smFRET distributions, consistent with a lack of well-defined secondary structure. Instead, our results show that phosphomimicry induces conformational rigidit...
-
Wavelet Shrinkage to Resolve Single Molecule FRET Structural Landscape of the Isolated Ligand Binding Domain of the AMPA Receptor
Biophysical Journal, 2011Co-Authors: Christy F. Landes, J. Nick Taylor, Anu Rambhadran, Vasanthi JayaramanAbstract:Single molecule fluorescence resonance energy transfer (smFRET) Spectroscopy has provided significant advances in our understanding of the relationship between structure and function in biological systems. Currently, simplifications must be made for experimental systems, data analysis, and theoretical modeling because biomolecules often exhibit mechanistic or conformational heterogeneity. For example, it is often necessary to treat biomolecular processes as transitions between two well-define states (e.g. folded vs. unfolded) despite clear experimental evidence or theoretical predictions to the contrary. The conformations explored by the agonist binding domain of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor represent such a system. The distribution of conformations in the raw data was so wide it was not possible to extract conformational details. By employing a model-free data analysis technique called wavelet shrinkage, it was determined that each protein form comprised multi-state, sequential equilibria. The results illustrate that the extent of activation is dependent not on a rigid closed cleft, but instead on the probability that a given subunit will occupy a closed cleft conformation, which in turn is determined by the range of states that the protein explores. Also, the results emphasize both the need for and the utility of advanced data processing techniques to quantify structure and dynamics in heterogeneous systems.
Chayan Dutta - One of the best experts on this subject based on the ideXlab platform.
-
Mechanistic Understanding of the Phosphorylation-Induced Conformational Rigidity at the AMPA Receptor C-terminal Domain
ACS omega, 2019Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Christy F. LandesAbstract:Phosphorylation at the intracellular C-terminal domain (CTD) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induces conformational rigidity. Such intracellular alterations to the AMPA receptor influence its functional responses, which are involved in multiple synaptic processes and neuronal signaling. The structure of the CTD still remains unresolved, which poses challenges toward providing a mechanism for the process of phosphorylation and deciphering the role of each phosphorylation step in causing the resultant conformational behavior. Herein, we utilize smFRET Spectroscopy to understand the mechanism of phosphorylation, with the help of strategic point mutations that mimic phosphorylation. Our results reveal that first, phosphorylation at three target sites (S818, S831, and T840) is necessary for the change in the secondary structure of the existing disordered native sequence. Also, the results suggest that the formation of the tertiary structure through electrostatic interac...
-
Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors
Journal of Physical Chemistry B, 2018Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Caitlin E. Nurik, Vasanthi Jayaraman, Christy F. LandesAbstract:The intracellular C-terminal domain (CTD) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor undergoes phosphorylation at specific locations during long-term potentiation. This modification enhances conductance through the AMPA receptor ion channel and thus potentially plays a crucial role in modulating receptor trafficking and signaling. However, because the CTD structure is largely unresolved, it is difficult to establish if phosphorylation induces conformational changes that might play a role in enhancing channel conductance. Herein, we utilize single-molecule Forster resonance energy transfer (smFRET) Spectroscopy to probe the conformational changes of a section of the AMPA receptor CTD, under the conditions of point-mutated phosphomimicry. Multiple analysis algorithms fail to identify stable conformational states within the smFRET distributions, consistent with a lack of well-defined secondary structure. Instead, our results show that phosphomimicry induces conformational rigidit...
Nicole C. Carrejo - One of the best experts on this subject based on the ideXlab platform.
-
Mechanistic Understanding of the Phosphorylation-Induced Conformational Rigidity at the AMPA Receptor C-terminal Domain
ACS omega, 2019Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Christy F. LandesAbstract:Phosphorylation at the intracellular C-terminal domain (CTD) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induces conformational rigidity. Such intracellular alterations to the AMPA receptor influence its functional responses, which are involved in multiple synaptic processes and neuronal signaling. The structure of the CTD still remains unresolved, which poses challenges toward providing a mechanism for the process of phosphorylation and deciphering the role of each phosphorylation step in causing the resultant conformational behavior. Herein, we utilize smFRET Spectroscopy to understand the mechanism of phosphorylation, with the help of strategic point mutations that mimic phosphorylation. Our results reveal that first, phosphorylation at three target sites (S818, S831, and T840) is necessary for the change in the secondary structure of the existing disordered native sequence. Also, the results suggest that the formation of the tertiary structure through electrostatic interac...
-
Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors
Journal of Physical Chemistry B, 2018Co-Authors: Sudeshna Chatterjee, Chayan Dutta, Nicole C. Carrejo, Caitlin E. Nurik, Vasanthi Jayaraman, Christy F. LandesAbstract:The intracellular C-terminal domain (CTD) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor undergoes phosphorylation at specific locations during long-term potentiation. This modification enhances conductance through the AMPA receptor ion channel and thus potentially plays a crucial role in modulating receptor trafficking and signaling. However, because the CTD structure is largely unresolved, it is difficult to establish if phosphorylation induces conformational changes that might play a role in enhancing channel conductance. Herein, we utilize single-molecule Forster resonance energy transfer (smFRET) Spectroscopy to probe the conformational changes of a section of the AMPA receptor CTD, under the conditions of point-mutated phosphomimicry. Multiple analysis algorithms fail to identify stable conformational states within the smFRET distributions, consistent with a lack of well-defined secondary structure. Instead, our results show that phosphomimicry induces conformational rigidit...