Abstract
The vacuolar protein sorting machinery regulates multivesicular body biogenesis and is selectively recruited by enveloped viruses to support budding. Here we report the crystal structure of the human ESCRT-III protein CHMP3 at 2.8 A resolution. The core structure of CHMP3 folds into a flat helical arrangement that assembles into a lattice, mainly via two different dimerization modes, and unilaterally exposes a highly basic surface. The C terminus, the target for Vps4-induced ESCRT disassembly, extends from the opposite side of the membrane targeting region. Mutations within the basic and dimerization regions hinder bilayer interaction in vivo and reverse the dominant-negative effect of a truncated CHMP3 fusion protein on HIV-1 budding. Thus, the final steps in the budding process may include CHMP protein polymerization and lattice formation on membranes by employing different bilayer-recognizing surfaces, a function shared by all CHMP family members.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acids, Acidic / chemistry
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Amino Acids, Basic / chemistry
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Conserved Sequence
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Crystallography, X-Ray*
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Dimerization
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Endosomal Sorting Complexes Required for Transport
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HIV Infections* / metabolism
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HIV Infections* / virology
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HIV-1 / physiology*
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Humans
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Hydrophobic and Hydrophilic Interactions
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Models, Molecular
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / metabolism
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Protein Structure, Secondary
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Protein Transport
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Sequence Homology, Amino Acid
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Static Electricity
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Vesicular Transport Proteins / chemistry*
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Vesicular Transport Proteins / genetics
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Vesicular Transport Proteins / metabolism*
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Virus Replication
Substances
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Amino Acids, Acidic
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Amino Acids, Basic
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CHMP3 protein, human
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Endosomal Sorting Complexes Required for Transport
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Nerve Tissue Proteins
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Recombinant Fusion Proteins
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Vesicular Transport Proteins