A Trimerizing GxxxG Motif Is Uniquely Inserted in the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Protein Transmembrane Domain
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- 作者：Eyal Arbely ; Zvi Granot ; Itamar Kass ; Joseph Orly ; Isaiah T. Arkin
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：September 26, 2006
- 年：2006
- 卷：45
- 期：38
- 页码：11349 - 11356
- 全文大小：492K
- 年卷期：v.45,no.38(September 26, 2006)
- ISSN：1520-4995
文摘
In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS)coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are uniqueto its proteins and not present in any other family member. We identified an insertion of two glycineresidues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which isnot found in any other coronavirus. This surprising finding raises an "oligomerization riddle": the GxxxGmotif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an invivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization isdriven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization ofthe entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-lengthprotein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike proteinTMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure,the glycine residues of the GxxxG motif are facing each other, enhancing helix-helix interactions byallowing for the close positioning of the helices. This unique orientation of the glycine residues alsostabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipidbilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiateother oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimericbundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxGmotif on this feature is discussed.