Comparison of the NMR and X‐ray structures of the HIV‐1 matrix protein: Evidence for conformational changes during viral assembly

• Published in: Protein science Vol. 5; no. 12; pp. 2391 - 2398
• Main Authors: Massiah, Michael A., Worthylake, David, Christensen, Allyson M., Sundquist, Wesley I., Hill, Christopher P., Summers, Michael F.
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01-12-1996
• Subjects: AIDS/HIV; Crystallography, X-Ray; gag Gene Products, Human Immunodeficiency Virus; Gene Products, gag - chemistry; Gene Products, gag - physiology; HIV Antigens - chemistry; HIV Antigens - physiology; human immunodeficiency virus type 1; Humans; Magnetic Resonance Spectroscopy; matrix protein; NMR spectroscopy; Protein Conformation; retroviral assembly; Viral Proteins; Virus Assembly; X‐ray crystallography
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.5560051202

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 Å displacement of a short 310 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 310 helix, serve as “hinges” that allow the 310 helix to undergo this structural reorientation.