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Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2-step entry mechanism

, : Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2-step entry mechanism. Faseb Journal 27(12): 5059-5071

Entry of enveloped viruses into host cells is mediated by their surface envelope glycoproteins (Env). On the surface of the virus, Env is in a metastable, prefusion state, primed to catalyze the fusion of the viral and host membranes. An external trigger is needed to promote the drastic conformational changes necessary for the fusion subunit to fold into the low-energy, 6-helix bundle. These triggers typically facilitate pH-independent entry at the plasma membrane or pH-dependent entry in a low-pH endosomal compartment. The α-retrovirus avian sarcoma leukosis virus (ASLV) has a rare, 2-step entry mechanism with both pH-dependent and pH-independent features. Here, we present the 2.0-Å-resolution crystal structure of the ASLV transmembrane (TM) fusion protein. Our structural and biophysical studies indicated that unlike other pH-dependent or pH-independent viral TMs, the ASLV fusion subunit is stable irrespective of pH. Two histidine residues (His490 and His492) in the chain reversal region confer stability at low pH. A structural comparison of class I viral fusion proteins suggests that the presence of a positive charge, either a histidine or arginine amino acid, stabilizes a helical dipole moment and is a signature of fusion proteins active at low pH. The structure now reveals key residues and features that explain its 2-step mechanism, and we discuss the implications of the ASLV TM structure in the context of general mechanisms required for membrane fusion.


PMID: 24036886

DOI: 10.1096/fj.13-232371

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Tu, L.C.en; Tu, H., 2000: Ablation apparatus for treating hemorrhoids. A medical apparatus for treating the hemorrhoid, or reducing the dilatation of tubular cellular tissues, wherein an elongate tubular shaft comprises at least one extendible wire means disposed at its distal end portion of the shaft to form a cylin...

Yang, C.S.; Lambert, J.D.; Hong, J.; Hou, J.Z.; Cullman, S.L.hman, 2003: Biotransformation and biological activities of tea polyphenols. Abstracts of Papers American Chemical Society 226(1-2): AGFD 43

Papini, M.P.trangeli; Majone, M.; Senofonte, O.; Caroli, S., 1994: Optimization of the analytical procedure for Cr, Cu, Ni, and Pb determination by ICP-AES in municipal landfill leachates. Microchemical Journal 50(2): 191-200

Heindl, L.M.; Schrödl, F.; Lütjen-Drecoll, E.; Cursiefen, C., 2013: Ciliary body lymphangiogenesis. Ophthalmology 120(7): E41-E42

Huang, W.; Chen, J., 2005: Analysis of odoriferous pollutants in cooling water by on-line LC-GC/FTIR method. The integration of two dimensional chromatography system (LC-GC) has ability for clean-up, enrichment, pre-separation and high resolution separation for the sample. The coupling of LC-GC with FTIR can notably improve the detection ability of conve...

Finkelstein, L.H.; Arsht, D.B.; Manfrey, S.J.; Childs, S., 1984: Ceftriaxone in the prevention of postoperative infection in patients undergoing transurethral resection of the prostate. One hundred twenty-nine patients undergoing transurethral resection of the prostate were treated preoperatively with either 1 g of ceftriaxone or placebo in a double-blind, randomized study. Sixty-three patients received placebo and 66 received ce...

Huancahuire-Vega, Són.; Ponce-Soto, L.Alberto.; Martins-de-Souza, D.; Marangoni, S., 2011: Biochemical and pharmacological characterization of PhTX-I a new myotoxic phospholipase A2 isolated from Porthidium hyoprora snake venom. This paper reports the biochemical and pharmacological characterization of a new myotoxic PLA(2) (EC called PhTX-I, purified from Porthidium hyoprora venom by one step analytical chromatography reverse phase HPLC. The homogeneity of the P...

D.M.ria, D.; Falchi, A.M.; Armaroli, L.; Balli, M.; Bortolus, R.; Busutti, L.; Busetto, M.; Polico, R.; Emiliani, E.; Maranzato, G., 1993: T-lymphocyte subsets in cancer patients undergoing radiotherapy and their recovery after thymostimulin treatment. A cooperative study. Rays 18(3): 438-453

Hofer, H.; Duncan, P., 1989: Field studies of growth in mammals: parental effort and potential fitness consequences. Unknown

Moore, W.; Renaudot, T., 2013: Remedy for all the inconveniences of life. Bmj 345: E8637-E8637