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Updated: Feb 2, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Structures of Ebola and Reston Virus VP35 Oligomerization Domains and Comparative Biophysical Characterization in All
Luca Zinzula1, István Nagy1, Massimiliano Orsini2
1The Max-Planck Institute of Biochemistry, Department of Molecular Structural Biology, Am Klopferspitz 18, 82152 Martinsried, Germany.
Abstract:
The multifunctional virion protein 35 (VP35) of ebolaviruses is a critical determinant of virulence and pathogenesis indispensable for viral replication and host innate immune evasion. Essential for VP35 function is homo-oligomerization via a coiled-coil motif. Here we report crystal structures of VP35 oligomerization domains from the prototypic Ebola virus (EBOV) and the non-pathogenic Reston virus (RESTV), together with a comparative biophysical characterization of the domains from all known species of the Ebolavirus genus. EBOV and RESTV VP35 oligomerization domains form bipartite parallel helix bundles with a canonical coiled coil in the N-terminal half and increased plasticity in the highly conserved C-terminal half. The domain assembles into trimers and tetramers in EBOV, whereas it exclusively forms tetramers in all other ebolavirus species. Substitution of coiled-coil leucine residues critical for immune antagonism leads to aberrant oligomerization. A conserved arginine involved in inter-chain salt bridges stabilizes the VP35 oligomerization domain and modulates between coiled-coil oligomeric states.
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