Structural and biophysical analysis of a tripartite ATP-independent periplasmic (TRAP) transporter.

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the -acetylneuraminate TRAP transporter (SiaQM) at 2.

Structure and mechanism of a tripartite ATP-independent periplasmic TRAP transporter.

In bacteria and archaea, tripartite ATP-independent periplasmic (TRAP) transporters uptake essential nutrients. TRAP transporters receive their substrates via a secreted soluble substrate-binding protein. How a sodium ion-driven secondary active transporter is strictly coupled to a substrate-binding protein is poorly understood.

Selective Nutrient Transport in Bacteria: Multicomponent Transporter Systems Reign Supreme.

Multicomponent transporters are used by bacteria to transport a wide range of nutrients. These systems use a substrate-binding protein to bind the nutrient with high affinity and then deliver it to a membrane-bound transporter for uptake. Nutrient uptake pathways are linked to the colonisation potential and pathogenicity of bacteria in humans and may be candidates for antimicrobial targeting.

Perceptual harmony in judgments of group prototypicality and intragroup respect.

We test common sense psychology of intragroup relations whereby people assume that intragroup respect and ingroup prototypicality are positively related. In Study 1a, participants rated a group member as more prototypical if they learned that group member was highly respected rather than disrespected. In Study 1b, participants rated a group member as more respected by other group members if they learned that group member was prototypical rather than unprototypical.

Identifying the "Therapy Targets" for Treating the Negative Symptoms of Psychosis Using Cognitive Behavioral Therapy.

The division of psychotic symptoms into positive and negative categories has largely divided the research on them. While the research on positive symptoms of psychosis has rapidly developed over the last three decades, the literature on negative symptoms has noticeably lagged behind. Negative symptoms have likely been ignored in the treatment literature because they were previously thought to remit following the treatment of positive symptoms.

Sleep and Mental Health in the General Population of Elderly Women.

Sleep and mental health complaints are prevalent in the elderly and share common risk factors. We assessed the relationship between sleep and mental health in three representative samples of elderly women while controlling for multiple risk factors common to both. We performed this cross sectional secondary data analysis in 2015 using 2013 data from the Behavioral Risk Factor Surveillance System (BRFSS) for females ages 65 years and older from California (N = 1912), Florida (N = 9120), and Pennsylvania (N = 2429).

Regulation of E2s: A Role for Additional Ubiquitin Binding Sites?

Attachment of ubiquitin to proteins relies on a sophisticated enzyme cascade that is tightly regulated. The machinery of ubiquitylation responds to a range of signals, which remarkably includes ubiquitin itself. Thus, ubiquitin is not only the central player in the ubiquitylation cascade but also a key regulator.

Noncovalent Ubiquitin Interactions Regulate the Catalytic Activity of Ubiquitin Writers.

Covalent modification of substrate proteins with ubiquitin is the end result of an intricate network of protein-protein interactions. The inherent ability of the E1, E2, and E3 proteins of the ubiquitylation cascade (the ubiquitin writers) to interact with ubiquitin facilitates this process. Importantly, contact between ubiquitin and the E2/E3 writers is required for catalysis and the assembly of chains of a given linkage.

Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity.

RING-domain E3 ligases enhance transfer of ubiquitin to substrate proteins by stabilizing the RING-bound thioester-linked E2∼ubiquitin conjugate in a defined conformation that primes the active site for nucleophilic attack. Here we report that the monomeric RING domains from the human E3 ligases Arkadia and Ark2C bind directly to free ubiquitin with an affinity comparable to that of other dedicated ubiquitin-binding domains. Further work showed that the Ark-like RING domain and the noncovalently bound ubiquitin molecule coordinately stabilize the E2-conjugated ubiquitin (donor ubiquitin) in the 'closed' conformation.