Human immunodeficiency virus type 1 matrix inhibits and confers cooperativity on gag precursor-membrane interactions.
Human immunodeficiency virus type 1 (HIV-1) Gag multimerization and membrane binding are required for particle formation. However, it is unclear what constitutes a minimal plasma membrane-specific targeting signal and what role the matrix (MA) globular head and other Gag domains play in membrane targeting. Here, we use membrane flotation and microscopic analysis of Gag deletion mutants to demonstrate that the HIV-1 MA globular head inhibits a plasma membrane-specific targeting signal contained within the six amino-terminal MA residues. MA-mediated inhibition is relieved by concentration-dependent Gag multimerization and imparts a high degree of cooperativity on Gag-membrane association. This cooperativity may confer temporal and spatial regulation on HIV-1 assembly.
Perez-Caballero
David
D
Aaron Diamond AIDS Research Center and the Rockefeller University, New York, New York 10016, USA.
Hatziioannou
Theodora
T
Martin-Serrano
Juan
J
Bieniasz
Paul D
PD
D000494:Allosteric Regulation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015683:Gene Products, gag / Q000737:chemistry / Q000378:metabolism*; D015488:HIV Antigens / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019814:Myristic Acid / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D019814:Myristic Acid