The three-dimensional solution-and solid-state structures of the human immunodeficiency virus type-1 (HIV-1) matrix protein have been determined recently in our laboratories by NMR and X-ray crystallographic methods (Massiah et al. 1994. J Mol Biol 244 : 198-223;Hill et al. 1996. Proc Natl Acad Sci USA 93:3099-3104). The matrix protein exists as a monomer in solution at low millimolar protein concentrations, but forms trimers in three different crystal lattices.Although the NMR and X-ray structures are similar, detailed comparisons have revealed an approximately 6 8, displacement of a short 3'0 helix (Pro 66-Gly 71) located at the trimer interface. High quality electron density and nuclear Overhauser effect (NOE) data support the integrity of the X-ray and NMR models, respectively. Because matrix apparently associates with the viral membrane as a trimer, displacement of the 310 helix may reflect a physiologically relevant conformational change that occurs during virion assembly and disassembly. These findings further suggest that Pro 66 and Gly 71, which bracket the 3'0 helix, serve as "hinges" that allow the 310 helix to undergo this structural reorientation.Keywords: human immunodeficiency virus type 1; matrix protein; NMR spectroscopy; retroviral assembly; X-ray crystallography The human immunodeficiency virus type-1 (HIV-I) genome encodes the structural Gag polyprotein (p55), which accumulates at the cell membrane during the late stages of the virus life cycle. Approximately 2,000 copies of the polyprotein assemble to form each immature virion. As these immature virions bud, the Gag polyproteins are cleaved by the viral protease into the three major viral structural proteins, matrix (MA, p17), capsid (CA, p24), and nucleocapsid (NC, p7), as well as three smaller peptide fragments (pl, p2, p6). These proteins subsequently undergo a major re- Abbreviations: HMQC-NOESY, heteronuclear multiple quantum coherence-nuclear Overhauser effect spectroscopy; NMR, nuclear magnetic resonance.arrangement, termed maturation, wherein the CA molecules condense to form the conical core particle that encapsidates the RNA-NC ribonucleoprotein complex, and the matrix proteins form a shell that remains associated with the inner face of the viral membrane (Gelderblom, 1991;Hoglund et al., 1992;Marx et al., 1988). Genetic analyses indicate that the matrix shell helps to anchor the transmembrane envelope protein (TM, gp41) on the surface of the virion, because mutations in both MA (Dorfman et al
