3C3O

ALIX Bro1-domain:CHMIP4A co-crystal structure

3C3O の概要

• エントリーDOI: 10.2210/pdb3c3o/pdb
• 関連するPDBエントリー: 2oew 3C3Q 3C3R
• 分子名称: Programmed cell death 6-interacting protein, Charged multivesicular body protein 4a peptide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: chmp4a alix bro1 amphipathic-helix, apoptosis, host-virus interaction, protein transport, transport, cytoplasmic vesicle, lipid-binding, membrane, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm, cytosol: Q8WUM4; Cytoplasmic vesicle membrane: Q9BY43
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44346.53

構造登録者

McCullough, J.B.,Fisher, R.D.,Whitby, F.G.,Sundquist, W.I.,Hill, C.P. (登録日: 2008-01-28, 公開日: 2008-06-10, 最終更新日: 2023-08-30)

主引用文献

McCullough, J.,Fisher, R.D.,Whitby, F.G.,Sundquist, W.I.,Hill, C.P.
ALIX-CHMP4 interactions in the human ESCRT pathway.
Proc.Natl.Acad.Sci.Usa, 105:7687-7691, 2008

PubMed Abstract: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis. To promote HIV budding and cytokinesis, the ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex, which in turn participate in essential membrane remodeling functions. Here, we report that the Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C). Crystal structures of the complexes reveal that the CHMP4 C-terminal peptides form amphipathic helices that bind across the conserved concave surface of ALIX(Bro1). ALIX-dependent HIV-1 budding is blocked by mutations in exposed ALIX(Bro1) residues that help contribute to the binding sites for three essential hydrophobic residues that are displayed on one side of the CHMP4 recognition helix (M/L/IxxLxxW). The homologous CHMP1-3 classes of ESCRT-III proteins also have C-terminal amphipathic helices, but, in those cases, the three hydrophobic residues are arrayed with L/I/MxxxLxxL spacing. Thus, the distinct patterns of hydrophobic residues provide a "code" that allows the different ESCRT-III subunits to bind different ESCRT pathway partners, with CHMP1-3 proteins binding MIT domain-containing proteins, such as VPS4 and Vta1/LIP5, and CHMP4 proteins binding Bro1 domain-containing proteins, such as ALIX.

PubMed: 18511562
DOI: 10.1073/pnas.0801567105

実験手法

X-RAY DIFFRACTION (2.15 Å)