Langya Henipavirus (LayV) infection is an emerging zoonotic disease that has been causing respiratory symptoms in China since 2019. For virus entry, LayV’s genome encodes the fusion protein F and the attachment glycoprotein G. However, the structural and functional information regarding LayV-G remains unclear. In this study, we revealed that LayV-G cannot bind to the receptors found in other HNVs, such as ephrin B2/B3, and it shows different antigenicity from HeV-G and NiV-G. Furthermore, we determined the near full-length structure of LayV-G, which displays a distinct mushroom-shaped configuration, distinguishing it from other attachment glycoproteins of HNV. The stalk and transmembrane regions resemble the stem and root of mushroom and four downward-tilted head domains as mushroom cap potentially interact with the F protein and influence membrane fusion process. Our findings enhance the understanding of emerging HNVs that cause human diseases through zoonotic transmission and provide implication for LayV related vaccine development.

SLC26A11, also known as the kidney and brain anion transporter (KBAT), mediates the transport of multiple anionic substrates across the plasma membrane. It is highly enriched in cerebellar Purkinje cells, where loss of KBAT results in hyperpolarized membrane potentials and increased intrinsic firing frequency, correlating with locomotor dysfunction. Despite its physiological significance, the molecular basis of substrate recognition and transport by KBAT remains elusive. Here, we present the structure of full-length human KBAT in an inward-facing conformation with chloride ions (Cl⁻) bound. Sequence analysis of the substrate-binding pockets uncovers the important residue E320 in KBAT. Protonation of E320 abolishes its interaction with S363 and correlates with Cl⁻ binding in the canonical substrate pocket, as substantiated by molecular dynamics (MD) simulations. Quantitative MD contact analysis delineates the rearrangements of residue interactions underlying the alternative access transport, consistent with an elevator-like transport mechanism. The cross-arranged transmembrane helices of the Gate and Core domains require minimal conformational rearrangement to achieve alternating access to the membrane. Collectively, our study provides a critical foundation for comprehensively understanding the recognition and transport mechanisms of human KBAT, with potential implications for developing therapies for neuronal swelling.

White adipose browning is a promising route to restore energy balance; however, how inorganic anion signals engage intracellular organelle networks to drive this process remains unclear. Here, we identify Sialin2 as a nitrate sensor that converts dietary nitrate into a spatially confined thermogenic program by coupling ER-mitochondria Ca²⁺ transfer with lipid routing into mitochondrial oxidation. Sialin2 localizes to mitochondria and the endoplasmic reticulum (ER), where it strengthens ER-mitochondria contacts and engages the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial calcium uniporter 1 (MCU1) conduit to enhance inducible mitochondrial Ca²⁺ uptake. In parallel, Sialin2 associates with lysosomal acid lipase (LIPA), acyl-CoA synthetase long-chain family member 3 (ACSL3), and carnitine palmitoyltransferase 1 A (CPT1A) to channel lipid-droplet-derived fatty acids into β-oxidation, thereby fueling the tricarboxylic acid cycle and uncoupling protein 1 (UCP1)-dependent respiration. Loss of Slc17a5 abolishes nitrate-evoked browning and metabolic benefits, whereas nitrate supplementation improves adipose thermogenesis and systemic metabolic indices in male mice with diet-induced obesity without adrenergic stimulation. Together, these findings identify an organelle-specific nitrate-sensing mechanism that couples inorganic anion signalling to substrate routing in adipocytes and establish a non-hormonal pathway for restoring metabolic homeostasis.