Molecular Sites for the Positive Allosteric Modulation of Glycine Receptors by Endocannabinoids
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Mendeley | Further Information

{"title"=>"Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids", "type"=>"journal", "authors"=>[{"first_name"=>"Gonzalo E.", "last_name"=>"Yévenes", "scopus_author_id"=>"6506335795"}, {"first_name"=>"Hanns Ulrich", "last_name"=>"Zeilhofer", "scopus_author_id"=>"35565098600"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"362415000", "isbn"=>"10.1371/journal.pone.0023886", "sgr"=>"80052056760", "issn"=>"19326203", "pmid"=>"21901142", "scopus"=>"2-s2.0-80052056760", "doi"=>"10.1371/journal.pone.0023886"}, "id"=>"b1a5ffb4-0703-3061-bde4-107c0373119b", "abstract"=>"Glycine receptors (GlyRs) are transmitter-gated anion channels of the Cys-loop superfamily which mediate synaptic inhibition at spinal and selected supraspinal sites. Although they serve pivotal functions in motor control and sensory processing, they have yet to be exploited as drug targets partly because of hitherto limited possibilities for allosteric control. Endocannabinoids (ECs) have recently been characterized as direct allosteric GlyR modulators, but the underlying molecular sites have remained unknown. Here, we show that chemically neutral ECs (e.g. anandamide, AEA) are positive modulators of α(1), α(2) and α(3) GlyRs, whereas acidic ECs (e.g. N-arachidonoyl-glycine; NA-Gly) potentiate α(1) GlyRs but inhibit α(2) and α(3). This subunit-specificity allowed us to identify the underlying molecular sites through analysis of chimeric and mutant receptors. We found that alanine 52 in extracellular loop 2, glycine 254 in transmembrane (TM) region 2 and intracellular lysine 385 determine the positive modulation of α(1) GlyRs by NA-Gly. Successive substitution of non-conserved extracellular and TM residues in α(2) converted NA-Gly-mediated inhibition into potentiation. Conversely, mutation of the conserved lysine within the intracellular loop between TM3 and TM4 attenuated NA-Gly-mediated potentiation of α(1) GlyRs, without affecting inhibition of α(2) and α(3). Notably, this mutation reduced modulation by AEA of all three GlyRs. These results define molecular sites for allosteric control of GlyRs by ECs and reveal an unrecognized function for the TM3-4 intracellular loop in the allosteric modulation of Cys-loop ion channels. The identification of these sites may help to understand the physiological role of this modulation and facilitate the development of novel therapeutic approaches to diseases such as spasticity, startle disease and possibly chronic pain.", "link"=>"http://www.mendeley.com/research/molecular-sites-positive-allosteric-modulation-glycine-receptors-endocannabinoids", "reader_count"=>33, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Other"=>5, "Student > Master"=>5, "Student > Bachelor"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Other"=>5, "Student > Master"=>5, "Student > Bachelor"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>6, "Neuroscience"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Chemistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Chile"=>2}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/743350"], "description"=>"<p>Values are indicated as mean ± s.e.m. from the indicated number of cells.</p><p>*indicates significant difference (P<0.05, ANOVA) against the corresponding wild type GlyR subtype.</p>", "links"=>[], "tags"=>["properties", "wild-type", "mutated"], "article_id"=>413728, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electrophysiological_properties_of_wild_type_and_mutated_GlyRs_/413728", "title"=>"Electrophysiological properties of wild-type and mutated GlyRs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-08-25 01:02:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/742582"], "description"=>"<p>(<b>A</b>) Primary sequence alignment between α<sub>1</sub> and α<sub>2</sub> GlyR subunits from TM1 to TM3 regions. The 3 non-conserved residues are highlighted by green boxes. (<b>B</b>) Examples of current traces through GlyRs with mutated TM domains, in absence (black) or presence of NA-Gly (red) (<b>C</b>) The bar graphs summarizes the normalized glycine-evoked current enhancement after the application of 10 µM NA-Gly on α<sub>1</sub> GlyRs with mutations in specific residues within the TM domains (<b>D</b>) Schematic representation of wild-type and TM2-mutated GlyRs (<b>E</b>) Concentration-response curves for NA-Gly in wild-type and TM-mutated α<sub>1</sub> and α<sub>2</sub> GlyRs using two different agonist concentrations. Note that the specific mutation G254A in α<sub>1</sub> GlyRs significantly attenuated the EC potentiation, whereas the reverse TM2 mutation in α<sub>2</sub> GlyRs (A261G) additionally decreased the NA-Gly-induced inhibition.</p>", "links"=>[], "tags"=>["na-gly", "allosteric", "glyrs", "influenced", "tm2"], "article_id"=>412962, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positive_and_negative_NA_Gly_allosteric_effects_on_1_and_945_2_GlyRs_are_influenced_by_a_single_TM2_domain_residue_/412962", "title"=>"Positive and negative NA-Gly allosteric effects on α<sub>1</sub> and α<sub>2</sub> GlyRs are influenced by a single TM2 domain residue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:49:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/742920"], "description"=>"<p>(<b>A</b>) Primary sequence alignment of α<sub>1</sub>, α<sub>2</sub> and α<sub>3</sub> GlyR subunits in selected extracellular loop 2, TM2 and TM3 segments (<b>B</b>) Schematic depiction of wild type and point mutated α<sub>3</sub> GlyRs. (<b>C</b>) Examples of current traces through wild-type and point-mutated α<sub>3</sub> GlyRs in absence (black) or presence of NA-Gly (10 µM, red) (<b>D</b>) Concentration-response curves for NA-Gly in wild-type and TM2-mutated α<sub>3</sub> GlyRs using two different glycine concentrations. Note that this specific mutation A265G in α<sub>3</sub> GlyRs significantly attenuated the NA-Gly-induced inhibition, but did not convert the inhibition into potentiation</p>", "links"=>[], "tags"=>["allosteric", "na-gly", "glyrs", "attenuated", "reverted", "altering", "tm2"], "article_id"=>413289, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g006", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_negative_allosteric_effects_of_NA_Gly_on_3_GlyRs_were_attenuated_but_not_reverted_by_altering_the_TM2_domain_composition_/413289", "title"=>"The negative allosteric effects of NA-Gly on α<sub>3</sub> GlyRs were attenuated but not reverted by altering the TM2 domain composition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:54:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/742663"], "description"=>"<p>(<b>A</b>) Amino acid sequence alignment between α<sub>1</sub> and α<sub>2</sub> GlyRs within the extracellular loop 2. The A52 residue in α<sub>1</sub> GlyRs and their homologous position in α<sub>2</sub> GlyRs are highlighted by a green box. (<b>B</b>) Schematic depictions of GlyRs with point mutations in the extracellular loop 2 (<b>C</b>) Concentration-response curves for NA-Gly in wild-type and extracellular loop 2-mutated α<sub>1</sub> and α<sub>2</sub> GlyRs using two different agonist concentrations. The mutation A52T significantly attenuated the NA-Gly sensitivity of α<sub>1</sub> GlyRs, whereas the reverse mutation in α<sub>2</sub> GlyRs (T59A) did not alter NAGly-induced inhibition.</p>", "links"=>[], "tags"=>["extracellular", "influences", "na-gly-induced", "potentiation"], "article_id"=>413034, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_composition_of_extracellular_loop_2_influences_the_NA_Gly_induced_potentiation_of_1_GlyRs_/413034", "title"=>"The composition of extracellular loop 2 influences the NA-Gly-induced potentiation of α<sub>1</sub> GlyRs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:50:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/743305"], "description"=>"<p>The schematic diagram summarizes the molecular sites for the allosteric modulation of GlyRs by acidic and neutral ECs. The inhibition of α<sub>2</sub> and α<sub>3</sub> GlyRs elicited by NA-Gly was specifically influenced by a single TM2 residue (A261 in α<sub>2</sub> GlyRs and A265 in α<sub>3</sub> GlyRs), whereas the NA-Gly-induced potentiation of α<sub>1</sub> GlyRs was reduced by mutating loop 2 (A52), TM2 (G254) or intracellular (K385) amino acids. On the other hand, the AEA-induced potentiation of these three GlyR subtypes was reduced by mutating a conserved intracellular lysine residue (K385 in α<sub>1</sub> GlyRs).</p>", "links"=>[], "tags"=>["sites", "allosteric", "modulation", "glyr", "subtypes"], "article_id"=>413677, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g009", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_sites_for_the_allosteric_modulation_of_different_GlyR_subtypes_by_ECs_/413677", "title"=>"Molecular sites for the allosteric modulation of different GlyR subtypes by ECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 01:01:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/743090"], "description"=>"<p>(<b>A</b>) The schematic receptor representation and the primary sequence alignment describe the position of the conserved intracellular K385 residue within the GlyR structure (<b>B</b>) Glycine-activated current traces from wild-type or K385A-mutated α<sub>1</sub> GlyRs before (black) and during the application of NA-Gly (5 µM, red) (<b>C</b>) Concentration-response curves for NA-Gly obtained from wild-type and K385-mutated GlyRs. The intracellular mutation significantly attenuated the NA-Gly-induced potentiation of α<sub>1</sub> GlyRs.</p>", "links"=>[], "tags"=>["allosteric", "modulation", "elicited", "na-gly", "influenced", "conserved", "lysine", "residue", "glyr", "intracellular"], "article_id"=>413454, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_positive_allosteric_modulation_elicited_by_NA_Gly_is_influenced_by_a_conserved_lysine_residue_within_the_1_GlyR_large_intracellular_loop_/413454", "title"=>"The positive allosteric modulation elicited by NA-Gly is influenced by a conserved lysine residue within the α<sub>1</sub> GlyR large intracellular loop.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:57:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/742765"], "description"=>"<p>(<b>A</b>) Examples of glycine-activated current traces from wild-type α<sub>1</sub> and mutant α<sub>2</sub> T59A/A261G/A303S GlyRs in the presence of NA-Gly (in red) (<b>B</b>) Summary of the effects of NA-Gly after simultaneous extracellular loop 2 and TM reverse mutations on α<sub>2</sub> GlyRs (*** P<0.001, vs α<sub>2</sub> GlyRs) (<b>C</b>) Schematic diagrams of the triple mutated α<sub>1</sub> and α<sub>2</sub> GlyRs (<b>D</b>) Sensitivity of the normalized glycine-activated currents elicited in wild-type and triple mutated GlyRs to different concentrations of NA-Gly. Note that three simultaneous reverse mutations in α<sub>2</sub> GlyR converted NA-Gly into an allosteric potentiator, whereas the homologous substitutions within α<sub>1</sub> GlyR still did not produce a significant inhibition.</p>", "links"=>[], "tags"=>["extracellular", "tm", "mutations", "glyrs", "na-gly", "allosteric"], "article_id"=>413135, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g005", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selective_extracellular_loop_2_and_TM_domain_mutations_in_2_GlyRs_convert_NA_Gly_into_an_allosteric_potentiator_/413135", "title"=>"Selective extracellular loop 2 and TM domain mutations in α<sub>2</sub> GlyRs convert NA-Gly into an allosteric potentiator.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:52:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/742448"], "description"=>"<p>(<b>A</b>) Schematic depiction of wild type and chimeric GlyRs. (<b>B</b>) Examples of whole-cell currents recorded from α<sub>1</sub>α<sub>2</sub> or α<sub>2</sub>α<sub>1</sub> GlyRs before (black) and during the application of NA-Gly (10 µM, red). (<b>C</b>) Percent change of the normalized glycinergic membrane currents during the application of NA-Gly (10 µM) using equipotent (EC<sub>10</sub>) glycine concentrations. The exchange of the IL between TM3 and TM4 plus the TM4 domain between α<sub>1</sub> and α<sub>2</sub> GlyRs did not significantly influence the NA-Gly-induced modulation.</p>", "links"=>[], "tags"=>["chimeric", "glyr"], "article_id"=>412825, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NA_Gly_effects_on_chimeric_GlyR_constructs_/412825", "title"=>"NA-Gly effects on chimeric GlyR constructs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:47:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/374460", "https://ndownloader.figshare.com/files/374545", "https://ndownloader.figshare.com/files/374637"], "description"=>"<div><p>Glycine receptors (GlyRs) are transmitter-gated anion channels of the Cys-loop superfamily which mediate synaptic inhibition at spinal and selected supraspinal sites. Although they serve pivotal functions in motor control and sensory processing, they have yet to be exploited as drug targets partly because of hitherto limited possibilities for allosteric control. Endocannabinoids (ECs) have recently been characterized as direct allosteric GlyR modulators, but the underlying molecular sites have remained unknown. Here, we show that chemically neutral ECs (e.g. anandamide, AEA) are positive modulators of α<sub>1</sub>, α<sub>2</sub> and α<sub>3</sub> GlyRs, whereas acidic ECs (e.g. N-arachidonoyl-glycine; NA-Gly) potentiate α<sub>1</sub> GlyRs but inhibit α<sub>2</sub> and α<sub>3</sub>. This subunit-specificity allowed us to identify the underlying molecular sites through analysis of chimeric and mutant receptors. We found that alanine 52 in extracellular loop 2, glycine 254 in transmembrane (TM) region 2 and intracellular lysine 385 determine the positive modulation of α<sub>1</sub> GlyRs by NA-Gly. Successive substitution of non-conserved extracellular and TM residues in α<sub>2</sub> converted NA-Gly-mediated inhibition into potentiation. Conversely, mutation of the conserved lysine within the intracellular loop between TM3 and TM4 attenuated NA-Gly-mediated potentiation of α<sub>1</sub> GlyRs, without affecting inhibition of α<sub>2</sub> and α<sub>3</sub>. Notably, this mutation reduced modulation by AEA of all three GlyRs. These results define molecular sites for allosteric control of GlyRs by ECs and reveal an unrecognized function for the TM3-4 intracellular loop in the allosteric modulation of Cys-loop ion channels. The identification of these sites may help to understand the physiological role of this modulation and facilitate the development of novel therapeutic approaches to diseases such as spasticity, startle disease and possibly chronic pain.</p> </div>", "links"=>[], "tags"=>["molecular", "sites", "allosteric", "modulation", "glycine", "receptors", "endocannabinoids"], "article_id"=>133948, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0023886.s001", "https://dx.doi.org/10.1371/journal.pone.0023886.s002", "https://dx.doi.org/10.1371/journal.pone.0023886.s003"], "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Molecular_Sites_for_the_Positive_Allosteric_Modulation_of_Glycine_Receptors_by_Endocannabinoids/133948", "title"=>"Molecular Sites for the Positive Allosteric Modulation of Glycine Receptors by Endocannabinoids", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-08-25 01:05:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/742325"], "description"=>"<p>(<b>A</b>) Glycine-activated membrane currents through wild-type α<sub>1</sub>, α<sub>2</sub> and α<sub>3</sub> GlyRs under control conditions (black) and in the presence of AEA, NA-Gly and VIR (red; all 10 µM). Membrane currents were activated by equipotent (EC<sub>10</sub>) glycine concentrations for each particular subunit. Chemical structures for the ligands are also shown. (<b>B</b>) Concentration-response curves. (<b>C</b>) Summary of the EC-mediated allosteric modulation of GlyRs subunits obtained at 10 µM concentration. Note that all acidic ECs tested still potentiated the α<sub>1</sub> GlyR currents, but inhibited currents through α<sub>2</sub> - α<sub>3</sub> GlyRs. NOLE, noladin ether; AEA, anandamide; NA-5HT, arachidonyl serotonin; NADA, N-arachidonyl dopamine, NA-Gly; N-arachidonyl glycine; NA-GABA, N-arachidonyl-GABA; NA-Ser, N-arachidonoyl-L-serine; NALA, N-arachidonoyl-L-alanine; AA, arachidonic acid; VIR, virodhamine. Data are means ± SEM from 6-15 cells.</p>", "links"=>[], "tags"=>["glyr", "subtypes"], "article_id"=>412701, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Modulation_of_different_GlyR_subtypes_by_ECs_/412701", "title"=>"Modulation of different GlyR subtypes by ECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:45:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/743228"], "description"=>"<p>(<b>A</b>) Examples of current traces through wild-type α<sub>1</sub> GlyRs and K385A mutated GlyRs in absence (black) or presence of AEA (5 µM, red) (<b>B</b>) Sensitivity to AEA of the normalized glycine-activated currents in wild-type and K385A-mutated GlyRs. The intracellular mutation effectively attenuated the AEA-induced modulation of the three GlyR subunits. (<b>C</b>) Glycine-activated current traces from wild-type or K385A-mutated α<sub>1</sub> GlyRs before (black) and during the application of NA-5HT (5 µM, red) (<b>D</b>) Concentration-response curves for NA-5HT obtained from wild-type and K385-mutated α<sub>1</sub> GlyRs (<b>E</b>) Summary of the allosteric effects elicited by AEA and NA-5HT in wild-type and K385A-mutated GlyRs. The current potentiation was significantly attenuated by the intracellular mutation. ***, P<0.001 between each wild-type GlyR and its corresponding K385A mutant.</p>", "links"=>[], "tags"=>["conserved", "intracellular", "lysine", "residue", "determines", "allosteric", "modulation", "ecs"], "article_id"=>413598, "categories"=>["Biochemistry", "Biophysics", "Pharmacology", "Molecular Biology", "Neuroscience", "Chemistry"], "users"=>["Gonzalo E. Yévenes", "Hanns Ulrich Zeilhofer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023886.g008", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_conserved_intracellular_lysine_residue_determines_the_positive_allosteric_modulation_by_neutral_ECs_on_GlyRs_/413598", "title"=>"A conserved intracellular lysine residue determines the positive allosteric modulation by neutral ECs on GlyRs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-08-25 00:59:58"}

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