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Abstract

Some of the best characterized alphaviruses are chikungunya virus (CHIKV), Semliki Forest virus (SFV) and Sindbis virus (SINV). E1 is a class II fusion protein, containing 3 domains (DI, DII, DIII) folded essentially as -sheet, plus a stem region connecting DIII to the transmembrane (TM) segment. The fusion loop (FL) is at the tip of the elongated DII. The X-ray structure of the SFV E1 post-fusion trimer, truncated of the stem region, displayed a tripod-shape with the DII legs open and the FLs away from each other, contrary to the class II viral fusion proteins from other viral genera, in which the FLs interact at the tip of the post-fusion trimer. Here, we set to identify if the stem plays a structural role in zippering together the E1 trimer to bring the fusion loops into contact.

We produced the recombinant ectodomains of E1 of CHIKV, SINV and SFV containing or not the stem, crystallized them and determined the X-ray structure.

We observed that CHIKV and SINV display E1 in closed conformation, in contrast to SFV, which displays a tripod even with the full stem. We identified a sequence motif in the stem responsible for the conformational difference.

Our results point to potential mechanistic differences between alphavirus E1 in driving fusion. Further functional studies are ongoing to pin-point the significance of these new findings, and the reasons for the alternative post-fusion conformations.

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/content/journal/acmi/10.1099/acmi.imav2019.po0061
2019-12-01
2020-01-27
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http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.imav2019.po0061
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