Li Fang, Berardi Marcelo, Li Wenhui, Farzan Michael, Dormitzer Philip R, Harrison Stephen C
Laboratory of Molecular Medicine, Children's Hospital, 320 Longwood Ave., Boston, MA 02115, USA.
J Virol. 2006 Jul;80(14):6794-800. doi: 10.1128/JVI.02744-05.
The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells.
严重急性呼吸综合征冠状病毒通过刺突蛋白（S）的活性进入细胞，该蛋白具有受体结合区（S1）和膜融合区（S2）。我们已对纯化的重组S胞外域（S-e）的四个连续状态进行了表征，该S-e包含S1和S2的胞外域。它们分别是S-e单体、未切割的S-e三聚体、切割后的S-e三聚体，以及解离的S1单体和S2三聚体玫瑰花结。降低pH值会诱导从柔性的L形S-e单体到丁香形三聚体的不可逆转变。三聚体的蛋白酶切割发生在S1-S2边界；随后的S1解离导致三聚体S2发生重大重排，并形成玫瑰花结，这些玫瑰花结可能代表通过其融合肽相连的S2延伸后融合三聚体的簇。S的状态和转变表明其构象变化介导了病毒进入细胞。
