Human Immunodeficiency Virus Type 1 Assembly, Release, and Maturation

NMR, Biophysical, and Biochemical Studies Reveal the Minimal Calmodulin Binding Domain of the HIV-1 Matrix Protein

“…Assembly of HIV-1 2 Gag occurs predominantly on the plasma membrane (PM), a step that is indispensable for proper and efficient assembly to produce progeny virions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Subsequent to virus assembly and budding, the virus undergoes a major morphological reorganization upon cleavage of the Gag polypeptides into several domains including the myristoylated matrix (myr(ϩ)MA), capsid, and nucleocapsid proteins (3,4,(17)(18)(19). Among the multiple functions proposed for the MA domain, its role in mediating Gag-membrane binding appears to be the most understood.…”

Binding of Calmodulin to the HIV-1 Matrix Protein Triggers Myristate Exposure

“…Gag binding to the PM is mediated by the MA domain and enhanced by multimerization. Proper assembly and efficient binding of Gag to the PM requires a myristyl (myr) group as a membrane anchor and a cluster of basic residues localized within the N-terminal domain to facilitate interactions with acidic phospholipids (1,2,19,20).Steady progress has been made in defining both the viral and cellular determinants of HIV-1 assembly and release (6). However, the trafficking pathway used by Gag to reach assembly sites in the infected cell is poorly understood.…”

“…Gag is the major structural protein encoded by HIV-1 and contains all of the viral elements required to drive virus assembly (1)(2)(3). HIV-1 Gag targeting to the plasma membrane (PM) 2 is critical for proper and efficient assembly to produce progeny virions (1,(3)(4)(5)(6)(7)(8)(9).…”

“…HIV-1 Gag targeting to the plasma membrane (PM) 2 is critical for proper and efficient assembly to produce progeny virions (1,(3)(4)(5)(6)(7)(8)(9). During virus maturation, Gag is cleaved into myristoylated matrix (myr(ϩ)MA), capsid, and nucleocapsid proteins, inducing major morphological reorganization of the virus (1,2,4,5,10). In many cell types, HIV-1 Gag budding and assembly has been shown to occur predominantly on the PM (4 -9, 11-18).…”

“…Gag binding to the PM is mediated by the MA domain and enhanced by multimerization. Proper assembly and efficient binding of Gag to the PM requires a myristyl (myr) group as a membrane anchor and a cluster of basic residues localized within the N-terminal domain to facilitate interactions with acidic phospholipids (1,2,19,20).…”