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Esser, T.

Publications and source records attributed to Esser, T..

2 recordsLinked to original sources

Membrane proteins retain native architecture through native ESI and soft-landing

Native MS offers a clear picture of membrane protein stoichiometry and interactions, but it lacks direct structural insights at high resolution. Here, we examine the extent to which solution-phase structure and architecture can be retained after native, soft-landing electrospray ion beam deposition (ESIBD) by interrogating several membrane-protein complexes of diverse folds and oligomeric states by cryoEM. The overall protein architectures with secondary structure motifs can be observed after gas-phase transfer, soft landing, and embedding in amorphous ice. Notably, we determined the structure of the ammonium transporter AmtB at sub-3 [A] resolution. It is nearly identical to the structure of the plunge-frozen control and even shows an extended C-terminal segment of AmtB, a dynamic region absent in the solution-phase structure. Our analysis shows that detergent adducts preserve membrane protein structure in vacuum by minimising destabilization of solvent-exposed regions and stabilization through additional polar contacts in vacuo. Molecular dynamics (MD) simulations support these results, suggesting that a monolayer shell of surfactant adducts avoids destabilization driven by unshielded polar residues and disruption of hydrogen bond networks. Overall, our findings provide a structural framework for integrating native MS with cryo-EM showing that gas-phase transfer and surfactant stabilisation preserves key architectural features and high-resolution structure of membrane proteins.

biophysics↗

Loneliness and the social brain: how perceived social isolation impairs human interactions

Loneliness is a painful condition associated with increased risk for premature mortality. The formation of new, positive social relationships can alleviate feelings of loneliness, but requires rapid trustworthiness decisions during initial encounters and it is still unclear how loneliness hinders interpersonal trust. Here, we use a multimodal approach including behavioral, psychophysiological, hormonal, and neuroimaging measurements to probe a trust-based mechanism underlying impaired social interactions in loneliness. Pre-stratified healthy individuals with high loneliness scores (n = 42 out of a screened sample of 3678 adults) show reduced oxytocinergic and affective responsiveness to a positive conversation, report less interpersonal trust, and prefer larger social distances compared to controls (n = 40). Moreover, lonely individuals are rated as less trustworthy compared to controls and identified by the blinded confederate better than chance. During initial trust decisions, lonely individuals exhibit attenuated limbic and striatal activation and blunted functional connectivity between the anterior insula and occipitoparietal regions, which correlates with the diminished affective responsiveness to the positive social interaction. This neural response pattern is not mediated by loneliness-associated psychological symptoms. Thus, our results indicate compromised integration of trust-related information as a shared neurobiological component in loneliness, yielding a reciprocally reinforced trust bias in social dyads.

neuroscience↗