Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) Na+/H+ antiporter.

Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na+ out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive. Here we elucidate two cryo-electron microscopy structures of rice (Oryza sativa) SOS1, a full-length protein in an auto-inhibited state and a truncated version in an active state. The SOS1 forms a dimeric architecture, with an NhaA-folded transmembrane domain portion in the membrane and an elongated cytosolic portion of multiple regulatory domains in the cytoplasm. The structural comparison shows that SOS1 adopts an elevator transport mechanism accompanied by a conformational transition of the highly conserved Pro148 in the unwound transmembrane helix 5 (TM5), switching from an occluded conformation in the auto-inhibited state to a conducting conformation in the active state. These findings allow us to propose an inhibition-release mechanism for SOS1 activation and elucidate how SOS1 controls Na+ homeostasis in response to salt stress.

Cryo-EM structure and electrophysiological characterization of ALMT from Glycine max reveal a previously uncharacterized class of anion channels.

Aluminum-activated malate transporters (ALMTs) form an anion channel family that plays essential roles in diverse functions in plants. Arabidopsis ALMT12, also named QUAC1 (quick anion channel 1), regulates stomatal closure in response to environmental stimuli. However, the molecular basis of ALMT12/QUAC1 activity remains elusive. Here, we describe the cryo-EM structure of ALMT12/QUAC1 from Glycine max at 3.5-Å resolution. GmALMT12/QUAC1 is a symmetrical dimer, forming a single electropositive T-shaped pore across the membrane. The transmembrane and cytoplasmic domains are assembled into a twisted two-layer architecture, with their associated dimeric interfaces nearly perpendicular. GmALMT12/QUAC1-mediated currents display rapid kinetics of activation/deactivation and a bell-shaped voltage dependency, reminiscent of the rapid (R)-type anion currents. Our structural and functional analyses reveal a domain-twisting mechanism for malate-mediated activation. Together, our study uncovers the molecular basis for a previously uncharacterized class of anion channels and provides insights into the gating and modulation of the ALMT12/QUAC1 anion channel.

Structure and activity of SLAC1 channels for stomatal signaling in leaves.

Stomata in leaves regulate gas exchange between the plant and its atmosphere. Various environmental stimuli elicit abscisic acid (ABA); ABA leads to phosphoactivation of slow anion channel 1 (SLAC1); SLAC1 activity reduces turgor pressure in aperture-defining guard cells; and stomatal closure ensues. We used electrophysiology for functional characterizations of Arabidopsis thaliana SLAC1 (AtSLAC1) and cryoelectron microscopy (cryo-EM) for structural analysis of Brachypodium distachyon SLAC1 (BdSLAC1), at 2.97-Å resolution. We identified 14 phosphorylation sites in AtSLAC1 and showed nearly 330-fold channel-activity enhancement with 4 to 6 of these phosphorylated. Seven SLAC1-conserved arginines are poised in BdSLAC1 for regulatory interaction with the N-terminal extension. This BdSLAC1 structure has its pores closed, in a basal state, spring loaded by phenylalanyl residues in high-energy conformations. SLAC1 phosphorylation fine-tunes an equilibrium between basal and activated SLAC1 trimers, thereby controlling the degree of stomatal opening.

Serum total bilirubin concentration is associated with carotid atherosclerosis in patients with prehypertension.

Objectives: Bilirubin has been demonstrated to be linked with anti-inflammatory and antioxidant progress. We aimed to evaluate the association between serum total bilirubin level and carotid intima-media thick-ness (cIMT) in patients with prehypertension. METHODS: We consecutively enrolled pre-hypertensive patients from a community in Guangzhou between January 2017 and January 2018. All patients underwent carotid artery ultrasonography measurement. The correlation between serum total bilirubin and cIMT was assessed by using the Pearson's correlation coefficient. Multiple logistic regression analysis was performed to assess the independent association between clinical parameters and carotid atherosclerosis. RESULTS: A total of 691 subjects with prehypertension were included in this study. There were 101 patients with increased cIMT (mean age 52.69 ± 11.58 years; 50 male) and 590 subjects with normal cIMT (mean age50.28 ± 10.33 years; 332 male). We found that cIMT was significantly related with systolic blood pressure(r = 0.257, P < 0.001), C-reactive protein (r = 0.327, P < 0.001), total cholesterol (r = 0.218, P = 0.002) and total bilirubin (r =-0.489, P < 0.001). A multiple logistic regression analysis revealed that total bilirubin was an independent factor for atherosclerosis (OR = 0.476; 95%CI: 0.253, 0.764; P < 0.001). CONCLUSION: Our results suggested that serum total bilirubin was inversely related with cIMT, and might be an early clinical marker for predicting the occurrence of subclinical carotid atherosclerosis in patients with prehypertension.