Biology subjects

Chen, Z.-W.

Publications and source records attributed to Chen, Z.-W..

3 recordsLinked to original sources

bioRxiv2020

Site-specific effects of neurosteroids on GABAA receptor activation and desensitization

This study examines how site-specific binding to the three identified neurosteroid binding sites in the 1{beta}3 GABAA receptor (GABAAR) contributes to neurosteroid allosteric modulation. We found that the potentiating neurosteroid, allopregnanolone, but not its inhibitory 3{beta}-epimer epi-allopregnanolone, binds to the canonical {beta}3(+)-1(-) intersubunit site that mediates receptor activation by neurosteroids. In contrast, both allopregnanolone and epi-allopregnanolone bind to intrasubunit sites in the {beta}3 subunit, promoting receptor desensitization and the 1 subunit promoting ligand-specific effects. Two neurosteroid analogues with diazirine moieties replacing the 3-hydroxyl (KK148 and KK150) bind to all three sites, but do not potentiate GABAAR currents. KK148 is a desensitizing agent, whereas KK150 is devoid of allosteric activity. These compounds provide potential chemical scaffolds for site-specific and general neurosteroid antagonists. Collectively, these data show that differential occupancy and efficacy at three discrete neurosteroid binding sites determine whether a neurosteroid has potentiating, inhibitory, or competitive antagonist activity on GABAARs.

biophysics↗

bioRxiv2019

Feeding intensity and molecular prey identification of the common long-armed octopus, Octopus minor (Mollusca: Octopodidae) in the wild

The common long-armed octopus, Octopus minor, is an important component of systems and supports the local fisheries in the coastal areas of northern China. And because of the overfishing, the national germplasm reserve was established as conservation area at the Moon Lake for the genetic resource of O.minor in 2012. For the fishery management and artificial breeding, especially for the management of exclusive conservation reserves, its role in the ecosystem requires assessment. Therefore, the feeding intensity of O. minor was studied from April to July 2014 when females reaching maturation, and prey composition was identified from stomach contents using a DNA barcoding method. Of the 172 sampled octopuses, 66 had stomach contents that were nearly digested into pulp. Maximum feeding intensity occurred during the month of April and the feeding intensity of the females was greater than that of the males in April and May. A considerable overall reduction of feeding intensity in both sexes occurred from April to July. A total of 8 species were identified as the prey of O. minor. Based on homology searches and phylogenetic analysis, of 60 sequences, 30 matched with fish (50.00%, by number), 13 with crustaceans (21.66%), one with annelid (1.66%), one with nematode (1.66%) and 15 with itself (25.00%). These results confirm that O. minor has habitual nature of strong dietary preference, with Gobiidae families (62.79%, by number) being an important prey during the time when females reach sexual maturation. From April to July, the observed cannibalism showed an increasing trend.

molecular biology↗

bioRxiv2018

Multiple Functional Neurosteroid Binding Sites on GABAA Receptors

Neurosteroids are endogenous modulators of neuronal excitability and nervous system development and are being developed as anesthetic agents and treatments for psychiatric diseases. While GABAA receptors are the primary molecular targets of neurosteroid action, the structural details of neurosteroid binding to these proteins remain ill-defined. We synthesized neurosteroid analogue photolabeling reagents in which the photolabeling groups were placed at three positions around the neurosteroid ring structure, enabling identification of binding sites and mapping of neurosteroid orientation within these sites. Using middle-down mass spectrometry, we identified three clusters of photolabeled residues representing three distinct neurosteroid binding sites in the human 1{beta}3 GABAA receptor. Novel intrasubunit binding sites were identified within the transmembrane helical bundles of both the 1 and {beta}3 subunits, adjacent to the extracellular domains. An intersubunit site in the interface between the {beta}3(+) and 1(-) subunits of the GABAA receptor pentamer was also identified. Computational docking studies of neurosteroid to the three sites predicted critical residues contributing to neurosteroid interaction with the GABAA receptors. Electrophysiological studies based on these predictions indicate that both the 1 intrasubunit and {beta}3-1 intersubunit sites are critical for neurosteroid action.

neuroscience↗