The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein.

The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis.

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence.

Structural basis of ligand binding modes of human EAAT2.

In the central nervous system (CNS), excitatory amino acid transporters (EAATs) mediate the uptake of excitatory neurotransmitter glutamate and maintain its low concentrations in the synaptic cleft for avoiding neuronal cytotoxicity. Dysfunction of EAATs can lead to many psychiatric diseases. Here we report cryo-EM structures of human EAAT2 in an inward-facing conformation, in the presence of substrate glutamate or selective inhibitor WAY-213613.

A novel three-TMH Na/H antiporter and the functional role of its oligomerization.

Na/Hantiportersare a category of ubiquitous transmembrane proteins with various important physiological roles in almost all living organisms ranging from bacteria to humans. However, the knowledge of novel Na/Hantiporters remains to be broadened, and the functional roles ofoligomerization in theseantiportershave not yet been thoroughly understood. Here, we reported functional analysis of an unknown transmembrane protein composed of 103 amino acid residues.

A Novel MFS-MDR Transporter, MdrP, Employs D223 as a Key Determinant in the Na Translocation Coupled to Norfloxacin Efflux.

Multidrug resistance (MDR) transporters of the major facilitator superfamily (MFS) were previously believed to drive the extrusion of multiple antimicrobial drugs through the coupling to proton translocation. Here, we present the identification of the first Na-coupled MFS-MDR transporter, MdrP, which also can achieve H-coupled drug efflux independently of Na. Importantly, we propose that MdrP can extrude norfloxacin in a mode of drug/Na antiport, which has not yet been reported in any MFS member.

An Uncharacterized Major Facilitator Superfamily Transporter From Exhibits Dual Functions as a Na(Li, K)/H Antiporter and a Multidrug Efflux Pump.

Within major facilitator superfamily (MFS), up to 27 unknown major facilitator families and many members of 60 well-characterized families have been functionally unknown as yet, due to their sharing no or significantly low sequence identity with characterized MFS members. Here we present the first report on the characterization of one functionally unknown MFS transporter designated MdrP with the accession version No. ANU18183.

Characterization of a Functionally Unknown Arginine-Aspartate-Aspartate Family Protein From and Functional Analysis of Its Conserved Arginine/Aspartate Residues.

Arginine-aspartate-aspartate (RDD) family, representing a category of transmembrane proteins containing one highly conserved arginine and two highly conserved aspartates, has been functionally uncharacterized as yet. Here we present the characterization of a member of this family designated RDD from the moderate halophile NEAU-ST10-40 and report for the first time that RDD should function as a novel Na(Li, K)/H antiporter. It's more interesting whether the highly conserved arginine/aspartate residues among the whole family or between RDD and its selected homologs are related to the protein function.

Characterization of a novel two-component Na(Li, K)/H antiporter from Halomonas zhaodongensis.

In this study, genomic DNA was screened for novel Na/H antiporter genes from Halomonas zhaodongensis by selection in Escherichia coli KNabc lacking three major Na/H antiporters. Co-expression of two genes designated umpAB, encoding paired homologous unknown membrane proteins belonging to DUF1538 (domain of unknown function with No. 1538) family, were found to confer E.

A novel NhaD-type Na/H antiporter from the moderate halophile and alkaliphile Halomonas alkaliphila.

In this study, a NhaD-type Na/H antiporter gene designated Ha-nhaD was obtained by selection of genomic DNA from the moderate halophile and alkaliphile Halomonas alkaliphila in Escherichia coli KNabc lacking 3 major Na/H antiporters. The presence of Ha-NhaD conferred tolerance of E. coli KNabc to NaCl up to 0.

Identification of dicalcium phosphate dihydrate deposited during osteoblast mineralization in vitro.

The hydroxyapatite (HAP) with variable chemical substitutions has been considered as the major component in the mineralized part of bones. Various metastable crystalline phases have been suggested as transitory precursors of HAP in bone, but there are no consensuses as to the nature of these phases and their temporal evolution. In the present study, we cultured rat calvarial osteoblasts with ascorbate and β-glycerophosphate to explore which calcium phosphate precursor phases comprise the initial mineral in the process of osteoblast mineralization in vitro.