No abstract

The capsaicin receptor TRPV1 has been intensively studied by cryo-electron microscopy and functional tests. However, though the apo and capsaicin-bound structural models are available, the dynamic process of capsaicin activation remains intangible, largely due to the lack of a capsaicin-induced open structural model and the low occupancy of the transition states. Here we report that reducing temperature toward the freezing point substantially increased channel closure events even in the presence of saturating capsaicin. We further used a combination of fluorescent unnatural amino acid (fUAA) incorporation, computational modeling, and rate-equilibrium linear free-energy relationships analysis (Φ-analysis) to derive the fully open capsaicin-bound state model, and reveal how the channel transits from the apo to the open state. We observed that capsaicin initiates a conformational wave that propagates through the S4–S5 linker towards the S6 bundle and finally reaching the selectivity filter. Our study provides a temporal mechanism for capsaicin activation of TRPV1.

This study examined how college students’ levels of planned happenstance skills influenced the relationships among career engagement, career decision self‐efficacy, and career decision certainty. Moderated mediation analysis was used with a sample of 217 Korean undergraduate students. The results indicated that career decision self‐efficacy mediated the relationship between career engagement and career decision certainty. Moreover, the positive indirect effect of career engagement on career decision through career decision self‐efficacy was strengthened as the level of planned happenstance skills increased. In conclusion, college students’ career engagement strengthens their career decision certainty via career decision self‐efficacy when they have enough planned happenstance skills to discover unexpected career opportunities.