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-Structure paper
タイトル | The prefusion structure of herpes simplex virus glycoprotein B. |
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ジャーナル・号・ページ | Sci Adv, Vol. 6, Issue 39, Year 2020 |
掲載日 | 2020年9月25日 |
著者 | B Vollmer / V Pražák / D Vasishtan / E E Jefferys / A Hernandez-Duran / M Vallbracht / B G Klupp / T C Mettenleiter / M Backovic / F A Rey / M Topf / K Grünewald / |
PubMed 要旨 | Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion ...Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins. |
リンク | Sci Adv / PubMed:32978151 / PubMed Central |
手法 | EM (サブトモグラム平均) |
解像度 | 9.1 Å |
構造データ | EMDB-11123: Pre-fusion conformation of glycoprotein B of Herpes simplex virus 1 |
由来 |
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キーワード | VIRAL PROTEIN / Membrane fusion protein / glycoprotein / gB / UL27 / viral entry protein / class III fusion protein / transmembrane protein / pre-fusion conformation |