Structural highlights
FunctionPublication Abstract from PubMedEbolavirus is an enveloped virus causing severe hemorrhagic fever. Its surface glycoproteins undergo proteolytic cleavage and rearrangements to permit membrane fusion and cell entry. Here we focus on the glycoprotein's internal fusion loop (FL), critical for low pH-triggered fusion in the endosome. Alanine mutations at L529, I544, and particularly the double mutant L529/I544 compromised viral entry and fusion. The NMR structures of I544A and L529A/I544A in lipid environments showed significant disruption of a three-residue scaffold that is required for the formation of a consolidated fusogenic hydrophobic surface at the tip of the FL. Biophysical experiments and molecular simulation revealed the position of the WT FL in membranes and showed the inability of the inactive double mutant to reach this position. Consolidation of hydrophobic residues at the tip of FLs may be a common requirement for internal FLs of class I, II, and III fusion proteins. IMPORTANCE:: Many class I, II, and III viral fusion proteins bear fusion loops for target membrane insertion and fusion. We determined structures of the Ebolavirus fusion loop and found residues critical for forming a consolidated hydrophobic surface, membrane insertion, and viral entry. Ebolavirus Entry Requires a Compact Hydrophobic Fist at the Tip of the Fusion Loop.,Gregory SM, Larsson P, Nelson EA, Kasson PM, White JM, Tamm LK J Virol. 2014 Apr 2. PMID:24696482[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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