4NPP: The GLIC-His10 wild-type structure in equilibrium between the open and locally-closed (LC) forms

Citation:
Abstract
Pentameric ligand-gated ion channels mediate fast chemical transmission of nerve signals. The structure of a bacterial proton-gated homolog has been established in its open and locally closed conformations at acidic pH. Here we report its crystal structure at neutral pH, thereby providing the X-ray structures of the two end-points of the gating mechanism in the same pentameric ligand-gated ion channel. The large structural variability in the neutral pH structure observed in the four copies of the pentamer present in the asymmetric unit has been used to analyze the intrinsic fluctuations in this state, which are found to prefigure the transition to the open state. In the extracellular domain (ECD), a marked quaternary change is observed, involving both a twist and a blooming motion, and the pore in the transmembrane domain (TMD) is closed by an upper bend of helix M2 (as in locally closed form) and a kink of helix M1, both helices no longer interacting across adjacent subunits. On the tertiary level, detachment of inner and outer beta sheets in the ECD reshapes two essential cavities at the ECD-ECD and ECD-TMD interfaces. The first one is the ligand-binding cavity; the other is close to a known divalent cation binding site in other pentameric ligand-gated ion channels. In addition, a different crystal form reveals that the locally closed and open conformations coexist as discrete ones at acidic pH. These structural results, together with site-directed mutagenesis, physiological recordings, and coarse-grained modeling, have been integrated to propose a model of the gating transition pathway.
PDB ID: 4NPPDownload
MMDB ID: 116303
PDB Deposition Date: 2013/11/22
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 3.35  Å
Source Organism:
Similar Structures:
Biological Unit for 4NPP: pentameric; determined by author and by software (PISA)
Molecular Components in 4NPP
Label Count Molecule
Proteins (5 molecules)
5
Proton-gated Ion Channel(Gene symbol: glr4197)
Molecule annotation
Chemicals (5 molecules)
1
5
* Click molecule labels to explore molecular sequence information.

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