Structural basis for budding by the ESCRT-III factor CHMP3.
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.
Muzioł
Tadeusz
T
European Molecular Biology Laboratory, 6 rue Jules Horowitz, 38042 Grenoble, France.
Pineda-Molina
Estela
E
Ravelli
Raimond B
RB
Zamborlini
Alessia
A
Usami
Yoshiko
Y
Göttlinger
Heinrich
H
Weissenhorn
Winfried
W
D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic / Q000737:chemistry; D024361:Amino Acids, Basic / Q000737:chemistry; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D056827:Endosomal Sorting Complexes Required for Transport; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D024342:Amino Acids, Acidic; D024361:Amino Acids, Basic; C498543:CHMP3 protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins