EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
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IF	>30 >20 >10 >5 all

タイトル	Palmitoylation Contributes to Membrane Curvature in Influenza A Virus Assembly and Hemagglutinin-Mediated Membrane Fusion.
ジャーナル・号・ページ	J Virol, Vol. 91, Issue 21, Year 2017
掲載日	2017年11月1日
著者	Petr Chlanda / Elena Mekhedov / Hang Waters / Alexander Sodt / Cindi Schwartz / Vinod Nair / Paul S Blank / Joshua Zimmerberg /
PubMed 要旨	The highly conserved cytoplasmic tail of influenza virus glycoprotein hemagglutinin (HA) contains three cysteines, posttranslationally modified by covalently bound fatty acids. While viral HA ...The highly conserved cytoplasmic tail of influenza virus glycoprotein hemagglutinin (HA) contains three cysteines, posttranslationally modified by covalently bound fatty acids. While viral HA acylation is crucial in virus replication, its physico-chemical role is unknown. We used virus-like particles (VLP) to study the effect of acylation on morphology, protein incorporation, lipid composition, and membrane fusion. Deacylation interrupted HA-M1 interactions since deacylated mutant HA failed to incorporate an M1 layer within spheroidal VLP, and filamentous particles incorporated increased numbers of neuraminidase (NA). While HA acylation did not influence VLP shape, lipid composition, or HA lateral spacing, acylation significantly affected envelope curvature. Compared to wild-type HA, deacylated HA is correlated with released particles with flat envelope curvature in the absence of the matrix (M1) protein layer. The spontaneous curvature of palmitate was calculated by molecular dynamic simulations and was found to be comparable to the curvature values derived from VLP size distributions. Cell-cell fusion assays show a strain-independent failure of fusion pore enlargement among H2 (A/Japan/305/57), H3 (A/Aichi/2/68), and H3 (A/Udorn/72) viruses. In contradistinction, acylation made no difference in the low-pH-dependent fusion of isolated VLPs to liposomes: fusion pores formed and expanded, as demonstrated by the presence of complete fusion products observed using cryo-electron tomography (cryo-ET). We propose that the primary mechanism of action of acylation is to control membrane curvature and to modify HA's interaction with M1 protein, while the stunting of fusion by deacylated HA acting in isolation may be balanced by other viral proteins which help lower the energetic barrier to pore expansion. Influenza A virus is an airborne pathogen causing seasonal epidemics and occasional pandemics. Hemagglutinin (HA), a glycoprotein abundant on the virion surface, is important in both influenza A virus assembly and entry. HA is modified by acylation whose removal abrogates viral replication. Here, we used cryo-electron tomography to obtain three-dimensional images to elucidate a role for HA acylation in VLP assembly. Our data indicate that HA acylation contributes to the capability of HA to bend membranes and to HA's interaction with the M1 scaffold protein during virus assembly. Furthermore, our data on VLP and, by hypothesis, virus suggests that HA acylation, while not critical to fusion pore formation, contributes to pore expansion in a target-dependent fashion.
リンク	J Virol / PubMed:28794042 / PubMed Central
手法	EM (トモグラフィー)
構造データ	EMDB-8843: Influenza A virus-like particles containing HA-MAY, NA, M1, and M2 proteins (MAY denotes three amino acids that replace three cysteine residues in the cytoplasmic tail of hemagglutinin) 手法: EM (トモグラフィー) EMDB-8844: Influenza A virus-like particles containing Hemagglutinin, Neuraminidase, M1, and M2 proteins 手法: EM (トモグラフィー) EMDB-8845: Influenza A virus-like particles containing Hemagglutinin, Neuraminidase, M1, and M2 proteins 手法: EM (トモグラフィー) EMDB-8846: Influenza A virus-like particles containing HA-MAY, NA, M1, and M2 proteins incubated with liposomes at pH 5 (MAY denotes three amino acids that replace three cysteines in the cytoplasmic tail of hemagglutinin) 手法: EM (トモグラフィー)