2H3Z

Structure of the HIV-1 matrix protein bound to di-C4-phosphatidylinositol-(4,5)-bisphosphate

2H3Z の概要

• エントリーDOI: 10.2210/pdb2h3z/pdb
• 関連するPDBエントリー: 2H3F 2H3I 2H3Q 2H3V
• 分子名称: Gag polyprotein, (2R)-3-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}PROPANE-1 ,2-DIYL DIBUTANOATE (2 entities in total)
• 機能のキーワード: hiv-1 unmyristoylated matrix protein, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P12497
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15368.97

構造登録者

Saad, J.S.,Miller, J.,Tai, J.,Kim, A.,Ghanam, R.H.,Summers, M.F. (登録日: 2006-05-23, 公開日: 2006-07-25, 最終更新日: 2024-05-01)

主引用文献

Saad, J.S.,Miller, J.,Tai, J.,Kim, A.,Ghanam, R.H.,Summers, M.F.
Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly.
Proc.Natl.Acad.Sci.Usa, 103:11364-11369, 2006

PubMed Abstract: During the late phase of HIV type 1 (HIV-1) replication, newly synthesized retroviral Gag proteins are targeted to the plasma membrane of most hematopoietic cell types, where they colocalize at lipid rafts and assemble into immature virions. Membrane binding is mediated by the matrix (MA) domain of Gag, a 132-residue polypeptide containing an N-terminal myristyl group that can adopt sequestered and exposed conformations. Although exposure is known to promote membrane binding, the mechanism by which Gag is targeted to specific membranes has yet to be established. Recent studies have shown that phosphatidylinositol (PI) 4,5-bisphosphate [PI(4,5)P(2)], a factor that regulates localization of cellular proteins to the plasma membrane, also regulates Gag localization and assembly. Here we show that PI(4,5)P(2) binds directly to HIV-1 MA, inducing a conformational change that triggers myristate exposure. Related phosphatidylinositides PI, PI(3)P, PI(4)P, PI(5)P, and PI(3,5)P(2) do not bind MA with significant affinity or trigger myristate exposure. Structural studies reveal that PI(4,5)P(2) adopts an "extended lipid" conformation, in which the inositol head group and 2'-fatty acid chain bind to a hydrophobic cleft, and the 1'-fatty acid and exposed myristyl group bracket a conserved basic surface patch previously implicated in membrane binding. Our findings indicate that PI(4,5)P(2) acts as both a trigger of the myristyl switch and a membrane anchor and suggest a potential mechanism for targeting Gag to membrane rafts.

PubMed: 16840558
DOI: 10.1073/pnas.0602818103
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実験手法

SOLUTION NMR