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Med Hypotheses 2021 Mar 30;151:110588. Epub 2021 Mar 30.

Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, Nicosia 99138, Cyprus; Animal Hospital, Diagnostic Laboratory, Faculty of Veterinary Medicine, Near East University, Nicosia 99138, Cyprus.

Daily new information emerges regarding the COVID-19, infection of SARS-CoV-2, which is considered a global pandemic. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are required to complete the viral invasion pathway and are present in the oral mucosa, gingiva and periodontal pocket. Thus, increasing the likelihood of periodontitis and gingivitis caused by COVID-19. Read More

J Mol Biol 2021 Apr 9:166986. Epub 2021 Apr 9.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing100101, China. Electronic address:

The outer membrane (OM) of Gram-negative bacteria, which consists of lipopolysaccharides (LPS) in the outer leaflet and phospholipids (PLs) in the inner leaflet, plays a key role in antibiotic resistance and pathogen virulence. The maintenance of lipid asymmetry (Mla) pathway is known to be involved in PL transport and contributes to the lipid homeostasis of the OM, yet the underlying molecular mechanism and the directionality of PL transport in this pathway remain elusive. Here, we reported the cryo-EM structures of the ATP-binding cassette (ABC) transporter MlaFEBD from P. Read More

Front Microbiol 2021 25;12:661524. Epub 2021 Mar 25.

INRAE, Univ. Bordeaux, Biologie du Fruit et Pathologie, UMR 1332, Villenave d'Ornon, France.

Although phytoplasma studies are still hampered by the lack of axenic cultivation methods, the availability of genome sequences allowed dramatic advances in the characterization of the virulence mechanisms deployed by phytoplasmas, and highlighted the detection of signal peptides as a crucial step to identify effectors secreted by phytoplasmas. However, various signal peptide prediction methods have been used to mine phytoplasma genomes, and no general evaluation of these methods is available so far for phytoplasma sequences. In this work, we compared the prediction performance of SignalP versions 3. Read More

Neoplasia 2021 Apr 8;23(4):415-428. Epub 2021 Apr 8.

Unit of Medical Genetics, Department of Biomedical Sciences (BIOMORF), University of Messina, Italy. Electronic address:

Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here that Trop-2 undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 and T88. Molecular modeling indicated that this cleavage induces a profound rearrangement of the Trop-2 structure, which suggested a deep impact on its biological function. Read More

Biochem Biophys Res Commun 2021 Apr 8;556:53-58. Epub 2021 Apr 8.

Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, 277-8561, Chiba, Japan; Center for Synchrotron Radiation Research, Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo-cho, 679-5198, Hyogo, Japan; AIST-UTokyo Advanced Operando-Measurement Technology Open Innovation Laboratory (OPERANDO-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 6-2-3 Kashiwanoha, Kashiwa, 277-8561, Chiba, Japan. Electronic address:

Interleukin 15 receptor (IL-15R) is a transmembrane signalling protein consisting of 3 subsets: α, β (IL-15Rβ), and γ (γ). IL-2 and IL-15 share the signalling domains IL-15Rβ and γ, although they bind to intrinsic α-subsets and non-signalling domains. Additionally, IL-2 and IL-15 play different roles; therefore, there have been many observations of the dynamic behaviours of IL-15R, which are linked to physiological functions. Read More

J Biol Chem 2021 Apr 8:100652. Epub 2021 Apr 8.

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232. Electronic address:

Processing of the amyloid precursor protein (APP) via the amyloidogenic pathway is associated with the etiology of Alzheimer's disease. The cleavage of APP by β-secretase to generate the transmembrane 99-residue C-terminal fragment (C99) and subsequent processing of C99 by γ-secretase to yield amyloid-β (Aβ) peptides are essential steps in this pathway. Biochemical evidence suggests amyloidogenic processing of C99 occurs in cholesterol- and sphingolipid-enriched liquid-ordered phase membrane rafts. Read More

J Biol Chem 2021 Jan 8;296:100269. Epub 2021 Jan 8.

Department of Chemistry, Michigan State University, East Lansing, Michigan, USA; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA. Electronic address:

ZIP4 is a representative member of the Zrt-/Irt-like protein (ZIP) transporter family and responsible for zinc uptake from diet. Loss-of-function mutations of human ZIP4 (hZIP4) drastically reduce zinc absorption, causing a life-threatening autosomal recessive disorder, acrodermatitis enteropathica (AE). These mutations occur not only in the conserved transmembrane zinc transport machinery, but also in the extracellular domain (ECD) of hZIP4, which is only present in a fraction of mammalian ZIPs. Read More

Biochem Biophys Res Commun 2021 Apr 6;556:9-15. Epub 2021 Apr 6.

Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address:

Lysosome-associated protein transmembrane 4α (LAPTM4α) is a four transmembrane-spanning protein primarily localized in endosomes and lysosomes and has several putative lysosomal targeting signals at its C-terminal cytoplasmic domain, including tyrosine-based motifs (YxxΦ) and PY motifs (L/PxxY). LAPTM4α has been previously shown to be ubiquitinated by the E3 ubiquitin ligase Nedd4-1 through binding to its PY motifs and sorted to lysosomes, however, the molecular mechanisms underlying the localization of LAPTM4α to endosomes/lysosomes have not yet been fully elucidated. In the present study, we show that LAPTM4α binds Nedd4-1 in a manner dependent on PY motifs, while the PY motifs and Nedd4-1 are not necessarily required for LAPTM4α ubiquitination. Read More

Immunology 2021 Apr 9. Epub 2021 Apr 9.

Institute for Biomedical Research (BIOMED), Laboratory of Cellular and Molecular Biology, National Scientific and Technical Research Council (CONICET), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina.

The impairment of the cystic fibrosis transmembrane conductance regulator (CFTR) activity induces intracellular chloride (Cl ) accumulation. The anion Cl , acting as a second messenger, stimulates the secretion of interleukin-1β (IL-1β), which starts an autocrine positive feedback loop. Here we show that NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) are indirectly modulated by the intracellular Cl concentration, showing maximal expression and activity at 75 mM Cl , in the presence of the ionophores nigericin and tributyltin. Read More

Front Immunol 2021 23;12:639818. Epub 2021 Mar 23.

Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.

Anti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge domain (HD) and the transmembrane domain (TMD) between the extracellular antigen-targeting CARs and the intracellular signaling modalities of CARs has not been systemically studied. In this study, a series of 19-CARs differing only by their HD (CD8, CD28, or IgG) and TMD (CD8 or CD28) was generated. Read More

Nat Cell Biol 2021 Apr 8;23(4):330-340. Epub 2021 Apr 8.

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China.

Biomolecular condensates (biocondensates) formed via liquid-liquid phase-separation of soluble proteins have been studied extensively. However, neither the phase-separation of endoplasmic reticulum (ER) transmembrane protein nor a biocondensate with organized membranous structures has been reported. Here, we have discovered a spherical ER membranous biocondensate with puzzle-like structures caused by condensation of the ER-resident stimulator of interferon genes (STING) in DNA virus-infected or 2'3'-cGAMP (cyclic GMP-AMP)-treated cells, which required STING transmembrane domains, an intrinsically disordered region (IDR) and a dimerization domain. Read More

Nat Commun 2021 Apr 8;12(1):2246. Epub 2021 Apr 8.

Department of Biochemistry and Molecular Biology, Institut de Biotecnologia i Biomedicina, Universitat de València, 46100, Burjassot, Spain.

Nat Commun 2021 04 7;12(1):2086. Epub 2021 Apr 7.

Laboratory of Receptor Structure and Signaling, The HIT Center for Life Sciences, Harbin Institute of Technology, Harbin, China.

Histamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human HR in complex with a G protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for G engagement in a model of "squash to activate and expand to deactivate". Read More

Mol Biol Cell 2021 Apr 7:mbcE20090590. Epub 2021 Apr 7.

Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill.

Lipid droplets (LDs) are neutral lipid-containing organelles enclosed in a single monolayer of phospholipids. LD formation begins with the accumulation of neutral lipids within the bilayer of the endoplasmic reticulum (ER) membrane. It is not known how the sites of formation of nascent LDs in the ER membrane are determined. Read More

Acta Crystallogr D Struct Biol 2021 Apr 3;77(Pt 4):391-402. Epub 2021 Mar 3.

Biomedical Research Institute (BIOMED), Catholic University of Argentina (UCA) - National Scientific and Technical Research Council (CONICET), C1107AFF Buenos Aires, Argentina.

Viral infection compromises specific organelles of the cell and readdresses its functional resources to satisfy the needs of the invading body. Around 70% of the coronavirus positive-sense single-stranded RNA encodes proteins involved in replication, and these viruses essentially take over the biosynthetic and transport mechanisms to ensure the efficient replication of their genome and trafficking of their virions. Some coronaviruses encode genes for ion-channel proteins - the envelope protein E (orf4a), orf3a and orf8 - which they successfully employ to take control of the endoplasmic reticulum-Golgi complex intermediate compartment or ERGIC. Read More

J Pept Sci 2021 Apr 6:e3327. Epub 2021 Apr 6.

Institute of Organic and Biomolecular Chemistry, Georg-August-University of Göttingen, Göttingen, Germany.

Peptide-mediated membrane fusion is frequently studied with in vitro bulk leaflet mixing assays based on Förster resonance energy transfer (FRET). In these, customized liposomes with fusogenic peptides are equipped with lipids which are labeled with fluorophores that form a FRET pair. Since FRET is dependent on distance and membrane fusion comes along with lipid mixing, the assays allow for conclusions on the membrane fusion process. Read More

Eur J Neurosci 2021 Apr 7. Epub 2021 Apr 7.

Neuroscience Center - HiLife, University of Helsinki, Finland.

Cholesterol is an essential constituent of cell membranes. The discovery of cholesterol recognition amino acid consensus (CRAC) motif in proteins indicated a putative direct, non-covalent interaction between cholesterol and proteins. In the present study, we evaluated the presence of a CRAC motif and its inverted version (CARC) in the transmembrane region (TMR) of the tyrosine kinase receptor family (RTK) in several species using in silico methods. Read More