Engineering the Effective p‑Type Dopant in GaAs/InAs Core–Shell Nanowires with Surface Dangling Bonds

Using first-principles calculation based on density-functional theory, we investigated the effect of surface dangling bond on p-type doping mechanism and the electronic structures in wurtzite (WZ) and zinc blende (ZB) GaAs/InAs core–shell nanowires (NWs) along the [0001] and [111] directions, respectively. The results of the formation energies show that the surface dangling bond of the In atom is a kind of stable defect. Both in WZ and ZB core–shell NWs, we found it is easier and more stable to realize dopant in the GaAs core. Moreover, the position of Cd impurity plays a key role in the formation of p-type nanowires. The farther the distance between the impurity and the surface dangling In atom, the easier it is to form the p-type characteristic of the nanowires. In particular, it shows an intrinsic behavior when doping the Cd impurity near the surface dangling bond. The surface dangling bonds have an ability to capture the holes from the neighbor doping impurity, resulting in the deactivation of dopants. Meanwhile, the transfer of hole moves the valence band down to the lower energy levels and even can lead to a band anticrossing phenomenon in the conduction band. Our results highlight a new physical coupling between the doped state and surface dangling bonds in GaAs/InAs core–shell NWs, and open a new opportunity for the development of tailoring nanoscale electronic properties

Structural basis of GABAB receptor–Gi protein coupling

International audienceG-protein-coupled receptors (GPCRs) have central roles in intercellular communication1,2. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABAB receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed with Gi1 protein. We found that a single G protein interacts with the GB2 subunit of the GABAB receptor at a site that mainly involves intracellular loop 2 on the side of the transmembrane domain. This is in contrast to the G protein binding in a central cavity, as has been observed with other classes of GPCR. This binding mode results from the active form of the transmembrane domain of this GABAB receptor being different from that of other GPCRs, as it shows no outside movement of transmembrane helix 6. Our work also provides details of the inter- and intra-subunit changes that link agonist binding to G-protein activation in this heterodimeric complex

Orthosteric and allosteric modulation of human HCAR2 signaling complex

Abstract Hydroxycarboxylic acids are crucial metabolic intermediates involved in various physiological and pathological processes, some of which are recognized by specific hydroxycarboxylic acid receptors (HCARs). HCAR2 is one such receptor, activated by endogenous β-hydroxybutyrate (3-HB) and butyrate, and is the target for Niacin. Interest in HCAR2 has been driven by its potential as a therapeutic target in cardiovascular and neuroinflammatory diseases. However, the limited understanding of how ligands bind to this receptor has hindered the development of alternative drugs able to avoid the common flushing side-effects associated with Niacin therapy. Here, we present three high-resolution structures of HCAR2-Gi1 complexes bound to four different ligands, one potent synthetic agonist (MK-6892) bound alone, and the two structures bound to the allosteric agonist compound 9n in conjunction with either the endogenous ligand 3-HB or niacin. These structures coupled with our functional and computational analyses further our understanding of ligand recognition, allosteric modulation, and activation of HCAR2 and pave the way for the development of high-efficiency drugs with reduced side-effects

Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor

Follicle stimulating hormone (FSH) is a glycoprotein hormone the functions of which are mediated by a G protein-coupled receptor, FSHR. Here, Duan et al. report cryo-EM structures of FSHR in active and inactive states, suggesting the molecular basis of FSH and small allosteric agonist-mediated FSHR activation

GPCRs steer G_i and G_s selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors

Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of Gs, Gi, or Gq proteins. The structural basis for G protein subtype selectivity by these GPCRs remains elusive. Here, we report the structures of the serotonin receptors 5-HT4, 5-HT6, and 5-HT7 with Gs, and 5-HT4 with Gi1. The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine receptor's selectivity for Gs and Gi, respectively. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures. Furthermore, we discover specific residues within TM5 and TM6 that function as micro-switches to form specific interactions with Gs or Gi. Together, these results present a common mechanism of Gs versus Gi protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin receptors