scholarly journals Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors

2018 ◽  
Vol 123 (1) ◽  
pp. 130-137 ◽  
Author(s):  
Sudeshna Chatterjee ◽  
Carina Ade ◽  
Caitlin E. Nurik ◽  
Nicole C. Carrejo ◽  
Chayan Dutta ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Conformational Rigidity ◽  
Terminal Domain

scholarly journals Correction to “Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors”

2019 ◽  
Vol 123 (5) ◽  
pp. 1214-1214
Author(s):  
Sudeshna Chatterjee ◽  
Carina Ade ◽  
Caitlin E. Nurik ◽  
Nicole C. Carrejo ◽  
Chayan Dutta ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Conformational Rigidity ◽  
Terminal Domain

scholarly journals Subunit-specific role for the amino-terminal domain of AMPA receptors in synaptic targeting

2017 ◽  
Vol 114 (27) ◽  
pp. 7136-7141 ◽  
Author(s):  
Javier Díaz-Alonso ◽  
Yujiao J. Sun ◽  
Adam J. Granger ◽  
Jonathan M. Levy ◽  
Sabine M. Blankenship ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Masking Effect ◽  
Synaptic Targeting ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Term Potentiation ◽  
Amino Terminal Domain

The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD. Remarkably, long-term potentiation (LTP) can override the masking effect of the GFP tag. GluA1, but not GluA2, lacking the ATD fails to show LTP. These findings uncover a role for the ATD in subunit-specific synaptic trafficking of AMPARs, both constitutively and during plasticity. How LTP, induced postsynaptically, engages these extracellular trafficking motifs and what specific cleft proteins participate in the process remain to be elucidated.

scholarly journals α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Channels Lacking the N-terminal Domain

2002 ◽  
Vol 277 (51) ◽  
pp. 49662-49667 ◽  
Author(s):  
Arja Pasternack ◽  
Sarah K. Coleman ◽  
Annukka Jouppila ◽  
David G. Mottershead ◽  
Maria Lindfors ◽  
...  
Keyword(s):  
Cell Surface ◽  
Ligand Binding ◽  
Ampa Receptor ◽  
Protein Interactions ◽  
Ampa Receptors ◽  
Terminal Domain ◽  
Gated Channel ◽  
Surface Ligand ◽  
Amino Acid Binding ◽  
G Protein Coupled

Ionotropic glutamate receptor (iGluR) subunits contain a ∼400-residue extracellular N-terminal domain (“X domain”), which is sequence-related to bacterial amino acid-binding proteins and to class C G-protein-coupled receptors. The X domain has been implicated in the assembly, transport to the cell surface, allosteric ligand binding, and desensitization in various members of the iGluR family, but its actual role in these events is poorly characterized. We have studied the properties of homomeric α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA)-selective GluR-D glutamate receptors carrying N-terminal deletions. Our analysis indicates that, surprisingly, transport to the cell surface, ligand binding properties, agonist-triggered channel activation, rapid desensitization, and allosteric potentiation by cyclothiazide can occur normally in the complete absence of the X domain (residues 22–402). The relatively intact ligand-gated channel function of a homomeric AMPA receptor in the absence of the X domain indirectly suggests more subtle roles for this domain in AMPA receptors,e.g.in the assembly of heteromeric receptors and in synaptic protein interactions.

scholarly journals Mapping the Interaction Sites between AMPA Receptors and TARPs Reveals a Role for the Receptor N-Terminal Domain in Channel Gating

Cell Reports ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. 728-740 ◽  
Author(s):  
Ondrej Cais ◽  
Beatriz Herguedas ◽  
Karolina Krol ◽  
Stuart G. Cull-Candy ◽  
Mark Farrant ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Channel Gating ◽  
Interaction Sites ◽  
Terminal Domain

scholarly journals The amino-terminal domain of GluA1 mediates LTP maintenance via interaction with neuroplastin-65

2021 ◽  
Vol 118 (9) ◽  
pp. e2019194118
Author(s):  
Chao-Hua Jiang ◽  
Mengping Wei ◽  
Chen Zhang ◽  
Yun Stone Shi
Keyword(s):  
Ampa Receptors ◽  
Cell Adhesion Molecule ◽  
Long Term Potentiation ◽  
Postsynaptic Membrane ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Term Potentiation ◽  
Amino Terminal Domain ◽  
Mutant Forms

Long-term potentiation (LTP) has long been considered as an important cellular mechanism for learning and memory. LTP expression involves NMDA receptor-dependent synaptic insertion of AMPA receptors (AMPARs). However, how AMPARs are recruited and anchored at the postsynaptic membrane during LTP remains largely unknown. In this study, using CRISPR/Cas9 to delete the endogenous AMPARs and replace them with the mutant forms in single neurons, we have found that the amino-terminal domain (ATD) of GluA1 is required for LTP maintenance. Moreover, we show that GluA1 ATD directly interacts with the cell adhesion molecule neuroplastin-65 (Np65). Neurons lacking Np65 exhibit severely impaired LTP maintenance, and Np65 deletion prevents GluA1 from rescuing LTP in AMPARs-deleted neurons. Thus, our study reveals an essential role for GluA1/Np65 binding in anchoring AMPARs at the postsynaptic membrane during LTP.

scholarly journals Crystal structure of the glutamate receptor GluA1 N-terminal domain

2011 ◽  
Vol 438 (2) ◽  
pp. 255-263 ◽  
Author(s):  
Guorui Yao ◽  
Yinong Zong ◽  
Shenyan Gu ◽  
Jie Zhou ◽  
Huaxi Xu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Protein Interactions ◽  
Ampa Receptors ◽  
Neurological Diseases ◽  
Protein Protein Interactions ◽  
Terminal Domain ◽  
The Central Nervous System ◽  
In Trans ◽  
Excitatory Neurotransmission ◽  
Active Channels

The AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subfamily of iGluRs (ionotropic glutamate receptors) is essential for fast excitatory neurotransmission in the central nervous system. The malfunction of AMPARs (AMPA receptors) has been implicated in many neurological diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. The active channels of AMPARs and other iGluR subfamilies are tetramers formed exclusively by assembly of subunits within the same subfamily. It has been proposed that the assembly process is controlled mainly by the extracellular ATD (N-terminal domain) of iGluR. In addition, ATD has also been implicated in synaptogenesis, iGluR trafficking and trans-synaptic signalling, through unknown mechanisms. We report in the present study a 2.5 Å (1 Å=0.1 nm) resolution crystal structure of the ATD of GluA1. Comparative analyses of the structure of GluA1-ATD and other subunits sheds light on our understanding of how ATD drives subfamily-specific assembly of AMPARs. In addition, analysis of the crystal lattice of GluA1-ATD suggests a novel mechanism by which the ATD might participate in inter-tetramer AMPAR clustering, as well as in trans-synaptic protein–protein interactions.

scholarly journals Mechanistic Understanding of the Phosphorylation-Induced Conformational Rigidity at the AMPA Receptor C-terminal Domain

ACS Omega ◽  
2019 ◽  
Vol 4 (10) ◽  
pp. 14211-14218
Author(s):  
Sudeshna Chatterjee ◽  
Chayan Dutta ◽  
Nicole C. Carrejo ◽  
Christy F. Landes
Keyword(s):  
Ampa Receptor ◽  
Conformational Rigidity ◽  
Terminal Domain ◽  
Mechanistic Understanding

Structure of clathrin cages and coats in ice

1986 ◽  
Vol 44 ◽  
pp. 94-97
Author(s):  
G.P.A. Vigers ◽  
R.A. Crowther ◽  
B.M.F. Pearse
Keyword(s):  
Electron Microscopy ◽  
Heavy Chain ◽  
Outer Part ◽  
Coated Vesicles ◽  
Eukaryotic Cells ◽  
Coat Proteins ◽  
Terminal Domain ◽  
Clathrin Heavy Chain ◽  
Membrane Components

Clathrin forms the polyhedral cage of coated vesicles, which mediate the transfer of selected membrane components within eukaryotic cells. Clathrin cages and coated vesicles have been extensively studied by electron microscopy of negatively stained preparations and shadowed specimens. From these studies the gross morphology of the outer part of the polyhedral coat has been established and some features of the packing of clathrin trimers into the coat have also been described. However these previous studies have not revealed any internal details about the position of the terminal domain of the clathrin heavy chain, the location of the 100kd-50kd accessory coat proteins or the interactions of the coat with the enclosed membrane.

Crystal structures of Magnaporthe oryzae trehalose-6-phosphate synthase (MoTps1) suggest a model for catalytic process of Tps1

2019 ◽  
Vol 476 (21) ◽  
pp. 3227-3240 ◽  
Author(s):  
Shanshan Wang ◽  
Yanxiang Zhao ◽  
Long Yi ◽  
Minghe Shen ◽  
Chao Wang ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Conformational Changes ◽  
Magnaporthe Oryzae ◽  
Structural Information ◽  
Complex Structure ◽  
Critical Role ◽  
Catalytic Process ◽  
Structural Basis ◽  
Salt Bridges ◽  
Terminal Domain

Trehalose-6-phosphate (T6P) synthase (Tps1) catalyzes the formation of T6P from UDP-glucose (UDPG) (or GDPG, etc.) and glucose-6-phosphate (G6P), and structural basis of this process has not been well studied. MoTps1 (Magnaporthe oryzae Tps1) plays a critical role in carbon and nitrogen metabolism, but its structural information is unknown. Here we present the crystal structures of MoTps1 apo, binary (with UDPG) and ternary (with UDPG/G6P or UDP/T6P) complexes. MoTps1 consists of two modified Rossmann-fold domains and a catalytic center in-between. Unlike Escherichia coli OtsA (EcOtsA, the Tps1 of E. coli), MoTps1 exists as a mixture of monomer, dimer, and oligomer in solution. Inter-chain salt bridges, which are not fully conserved in EcOtsA, play primary roles in MoTps1 oligomerization. Binding of UDPG by MoTps1 C-terminal domain modifies the substrate pocket of MoTps1. In the MoTps1 ternary complex structure, UDP and T6P, the products of UDPG and G6P, are detected, and substantial conformational rearrangements of N-terminal domain, including structural reshuffling (β3–β4 loop to α0 helix) and movement of a ‘shift region' towards the catalytic centre, are observed. These conformational changes render MoTps1 to a ‘closed' state compared with its ‘open' state in apo or UDPG complex structures. By solving the EcOtsA apo structure, we confirmed that similar ligand binding induced conformational changes also exist in EcOtsA, although no structural reshuffling involved. Based on our research and previous studies, we present a model for the catalytic process of Tps1. Our research provides novel information on MoTps1, Tps1 family, and structure-based antifungal drug design.

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