8FE1

Alpha1/BetaB Heteromeric Glycine Receptor in 1 mM Glycine 20 uM Ivermectin State


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.00 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Conformational transitions and allosteric modulation in a heteromeric glycine receptor.

Gibbs, E.Klemm, E.Seiferth, D.Kumar, A.Ilca, S.L.Biggin, P.C.Chakrapani, S.

(2023) Nat Commun 14: 1363-1363

  • DOI: https://doi.org/10.1038/s41467-023-37106-7
  • Primary Citation of Related Structures:  
    8FE1

  • PubMed Abstract: 

    Glycine Receptors (GlyRs) provide inhibitory neuronal input in the spinal cord and brainstem, which is critical for muscle coordination and sensory perception. Synaptic GlyRs are a heteromeric assembly of α and β subunits. Here we present cryo-EM structures of full-length zebrafish α1β B GlyR in the presence of an antagonist (strychnine), agonist (glycine), or agonist with a positive allosteric modulator (glycine/ivermectin). Each structure shows a distinct pore conformation with varying degrees of asymmetry. Molecular dynamic simulations found the structures were in a closed (strychnine) and desensitized states (glycine and glycine/ivermectin). Ivermectin binds at all five interfaces, but in a distinct binding pose at the β-α interface. Subunit-specific features were sufficient to solve structures without a fiduciary marker and to confirm the 4α:1β stoichiometry recently observed. We also report features of the extracellular and intracellular domains. Together, our results show distinct compositional and conformational properties of α 1 βGlyR and provide a framework for further study of this physiologically important channel.


  • Organizational Affiliation

    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106-4970, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glycine receptor subunit alphaZ1A,
B [auth D],
C,
D [auth B]
458Danio rerioMutation(s): 0 
Gene Names: glra1
Membrane Entity: Yes 
UniProt
Find proteins for O93430 (Danio rerio)
Explore O93430 
Go to UniProtKB:  O93430
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO93430
Glycosylation
Glycosylation Sites: 1
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Glycine receptor beta subunit 2591Danio rerioMutation(s): 0 
Gene Names: glrb2zgc:101041glrbbSO:0001217
Membrane Entity: Yes 
UniProt
Find proteins for Q6DC22 (Danio rerio)
Explore Q6DC22 
Go to UniProtKB:  Q6DC22
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6DC22
Glycosylation
Glycosylation Sites: 2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IVM (Subject of Investigation/LOI)
Query on IVM

Download Ideal Coordinates CCD File 
FA [auth C],
H [auth A],
I [auth A],
QA [auth B],
R [auth D]
(2aE,4E,5'S,6S,6'R,7S,8E,11R,13R,15S,17aR,20R,20aR,20bS)-6'-[(2S)-butan-2-yl]-20,20b-dihydroxy-5',6,8,19-tetramethyl-17 -oxo-3',4',5',6,6',10,11,14,15,17,17a,20,20a,20b-tetradecahydro-2H,7H-spiro[11,15-methanofuro[4,3,2-pq][2,6]benzodioxacy clooctadecine-13,2'-pyran]-7-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-alpha-L-arabino-hexopyranosyl)-3-O-methyl-alpha-L-arabino-hexopyranoside
C48 H74 O14
AZSNMRSAGSSBNP-XPNPUAGNSA-N
PX4
Query on PX4

Download Ideal Coordinates CCD File 
CA [auth C]
HA [auth C]
J [auth A]
OA [auth B]
RA [auth B]
CA [auth C],
HA [auth C],
J [auth A],
OA [auth B],
RA [auth B],
S [auth D],
U [auth D],
ZA [auth E]
1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
C36 H73 N O8 P
CITHEXJVPOWHKC-UUWRZZSWSA-O
PLM
Query on PLM

Download Ideal Coordinates CCD File 
AA [auth D]
BB [auth E]
CB [auth E]
DB [auth E]
EB [auth E]
AA [auth D],
BB [auth E],
CB [auth E],
DB [auth E],
EB [auth E],
FB [auth E],
IA [auth C],
JA [auth C],
KA [auth C],
L [auth A],
LA [auth C],
M [auth A],
MA [auth C],
N [auth A],
NA [auth C],
O [auth A],
P [auth A],
SA [auth B],
T [auth D],
TA [auth B],
UA [auth B],
VA [auth B],
W [auth D],
WA [auth B],
X [auth D],
XA [auth B],
Y [auth D],
Z [auth D]
PALMITIC ACID
C16 H32 O2
IPCSVZSSVZVIGE-UHFFFAOYSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AB [auth E]
EA [auth C]
G [auth A]
PA [auth B]
Q [auth D]
AB [auth E],
EA [auth C],
G [auth A],
PA [auth B],
Q [auth D],
YA [auth E]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
D10
Query on D10

Download Ideal Coordinates CCD File 
GA [auth C]DECANE
C10 H22
DIOQZVSQGTUSAI-UHFFFAOYSA-N
GLY (Subject of Investigation/LOI)
Query on GLY

Download Ideal Coordinates CCD File 
BA [auth C],
DA [auth C],
F [auth A],
K [auth A],
V [auth D]
GLYCINE
C2 H5 N O2
DHMQDGOQFOQNFH-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.00 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONcryoSPARC3.3.2

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States1F32GM142233
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR35GM134896
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR35GM134896-2S1

Revision History  (Full details and data files)

  • Version 1.0: 2023-03-22
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Data collection, Database references
  • Version 1.2: 2024-06-12
    Changes: Database references
  • Version 1.3: 2024-10-30
    Changes: Data collection, Structure summary