@article {65286,
	title = {Structure and assembly of calcium homeostasis modulator proteins.},
	journal = {Nature Structural and Molecular Biology},
	volume = {27},
	year = {2020},
	month = {2020 Jan 27},
	pages = {150-9},
	abstract = {<p>The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), through which ions and ATP permeate in a voltage-dependent manner to control neuronal excitability, taste signaling and pathologies of depression and Alzheimer{\textquoteright}s disease. Despite such critical biological roles, the structures and patterns of their oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single-particle cryo-electron microscopy (cryo-EM), which show novel assembly of the four transmembrane helices into channels of octamers and undecamers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore size, lipid accommodation and channel activity.</p>
},
	issn = {1545-9985},
	doi = {10.1038/s41594-019-0369-9},
	author = {Syrjanen, Johanna L and Michalski, Kevin and Chou, Tsung-Han and Grant, Timothy and Rao, Shanlin and Simorowski, Noriko and Tucker, Stephen J and Grigorieff, Nikolaus and Furukawa, Hiro}
}
@article {47509,
	title = {Activation of NMDA receptors and the mechanism of inhibition by ifenprodil.},
	journal = {Nature},
	volume = {534},
	year = {2016},
	month = {2016 Jun 2},
	pages = {63-8},
	abstract = {<p>The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed mainly of GluN1 and GluN2 subunits. Activation of NMDA receptors requires binding of neurotransmitter agonists to a ligand-binding domain (LBD) and structural rearrangement of an amino-terminal domain (ATD). Recent crystal structures of GluN1-GluN2B NMDA receptors bound to agonists and an allosteric inhibitor, ifenprodil, represent the allosterically inhibited state. However, how the ATD and LBD move to activate the NMDA receptor ion channel remains unclear. Here we applied X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to rat NMDA receptors to show that, in the absence of ifenprodil, the bi-lobed structure of GluN2 ATD adopts an open conformation accompanied by rearrangement of the GluN1-GluN2 ATD heterodimeric interface, altering subunit orientation in the ATD and LBD and forming an active receptor conformation that gates the ion channel.</p>
},
	issn = {1476-4687},
	doi = {10.1038/nature17679},
	author = {Tajima, Nami and Karakas, Erkan and Grant, Timothy and Simorowski, Noriko and Diaz-Avalos, Ruben and Grigorieff, Nikolaus and Furukawa, Hiro}
}
