The bile acid-sensitive ion channel is gated by Ca-dependent conformational changes in the transmembrane domain.

The bile acid-sensitive ion channel (BASIC) is the least understood member of the mammalian epithelial Na channel/degenerin (ENaC/DEG) superfamily of ion channels, which are involved in a variety of physiological processes. While some members of this superfamily, including BASIC, are inhibited by extracellular Ca (Ca ), the molecular mechanism underlying Ca modulation remains unclear. Here, by determining the structure of human BASIC in the presence and absence of Ca using single particle cryo-electron microscopy (cryo-EM), we reveal Ca-dependent conformational changes in the transmembrane domain and β-linkers.

Cryo-electron tomographic investigation of native hippocampal glutamatergic synapses.

Chemical synapses are the major sites of communication between neurons in the nervous system and mediate either excitatory or inhibitory signaling. At excitatory synapses, glutamate is the primary neurotransmitter and upon release from presynaptic vesicles, is detected by postsynaptic glutamate receptors, which include ionotropic AMPA and NMDA receptors. Here, we have developed methods to identify glutamatergic synapses in brain tissue slices, label AMPA receptors with small gold nanoparticles (AuNPs), and prepare lamella for cryo-electron tomography studies.

Structure of the human dopamine transporter and mechanisms of inhibition.

The neurotransmitter dopamine has central roles in mood, appetite, arousal and movement. Despite its importance in brain physiology and function, and as a target for illicit and therapeutic drugs, the human dopamine transporter (hDAT) and mechanisms by which it is inhibited by small molecules and Zn are without a high-resolution structural context. Here we determine the structure of hDAT in a tripartite complex with the competitive inhibitor and cocaine analogue, (-)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane (β-CFT), the non-competitive inhibitor MRS7292 and Zn (ref.

The structure of the TMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction.

Mechanotransduction is the process by which a mechanical force, such as touch, is converted into an electrical signal. Transmembrane channel-like (TMC) proteins are an evolutionarily conserved family of membrane proteins whose function has been linked to a variety of mechanosensory processes, including hearing and balance sensation in vertebrates and locomotion in . TMC1 and TMC2 are components of ion channel complexes, but the molecular features that tune these complexes to diverse mechanical stimuli are unknown.

Single molecule studies of the native hair cell mechanosensory transduction complex.

Hearing and balance rely on the conversion of a mechanical stimulus into an electrical signal, a process known as mechanosensory transduction (MT). In vertebrates, this process is accomplished by an MT complex that is located in hair cells of the inner ear. While the past three decades of research have identified many subunits that are important for MT and revealed interactions between these subunits, the composition and organization of a functional complex remains unknown.