No abstract

Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds to KRS, impinged on interaction of KRS with 67LR and suppressed metastasis in 3 different mouse models. The compound inhibited KRS–67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS–67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.

Spherical black carbon aggregates were frequently observed in dust dry deposition in Daejeon, Korea. They were tens of micrometers in diameter and presented a mixture of black carbon and several mineral phases. Transmission electron microscopy (TEM) observations with energy-dispersive X-ray spectroscopy (EDS) and selected area diffraction pattern (SADP) analyses confirmed that the aggregates were compact and included significant amounts of lead chromate (PbCrO4). The compositions and morphologies of the nanosized lead chromate particles suggest that they probably originated from traffic paint used in roads and were combined as discrete minerals with black carbon. Based on Pb isotope analysis and air-mass backward trajectories, the dust in Daejeon received a considerable input of anthropogenic pollutants from heavily industrialized Chinese cities, which implies that long-range transported aerosols containing PbCrO4 were a possible source of the lead and hexavalent chromium levels in East Asia. Lead chromate should be considered to be a source of global atmospheric Pb and Cr(VI) pollution, especially given its toxicity.

a b s t r a c tLysyl-tRNA synthetase (KRS) interacts with the laminin receptor (LR/RPSA) and enhances laminininduced cell migration in cancer metastasis. In this nuclear magnetic resonance (NMR)-based study, we show that the anticodon-binding domain of KRS binds directly to the C-terminal region of 37LRP, and the previously found inhibitors BC-K-01 and BC-K-YH16899 interfere with KRS-37LRP binding. In addition, the anticodon-binding domain of KRS binds to laminin, observed by NMR and SPR. These results provide crucial insights into the structural characteristics of the KRS-LR interaction on the cell surface. Structured summary of protein interactions:KRS-ABD binds to 37LRP by surface plasmon resonance (View interaction) KRS-ABD and 37LRP bind by nuclear magnetic resonance (1, 2, 3) 37LRP and KRS-ABD bind by molecular sieving (View interaction) KRS-ABD and laminin peptide bind by nuclear magnetic resonance (View interaction) Ó