Solution Structures of Engineered Vault Particles
26 Pages Posted: 11 Apr 2018 Publication Status: PublishedMore...
Prior crystal structures of the vault have provided clues of its structural variability but are non-conclusive due to crystal packing. Here, we obtained vaults by engineering at the N-terminus of rat major vault protein (MVP) an HIV-1 Gag protein segment and determined their near-atomic resolution structures in non-crystalline/solution environment. Vaults in solution adopt two conformations, 1 and 2, both with D39 symmetry. From N- to C-terminus, each MVP monomer is organized into three regions: body, shoulder and cap. While conformer 1 is identical to one of the crystal structures, the shoulder in conformation 2 is translocated up to 10 Å along the symmetry axis, resulting in an outward-projected cap. Our structures clarify the conformation discrepancies in the body domain in the prior crystallography models. The vault’s drug-delivery potential is highlighted by the internal localization and structural flexibility of its Gag-loaded N-terminal extension at the waist region of the engineered vault.
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