- 作者: Hung-Hao Chu; Yu-Fen Chang; Chin-Tien Wang
- 作者服務機構: 1 Department of Medical Research and Education, Taipei Veterans General Hospital, 201, Sec. 2, Shih-Pai Road, Taipei, 11217, Taiwan; ; 2 Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: The X-ray crystallographic structure of HIV-1 capsid protein suggests that the dimer interface of the dimerization domain is mainly formed from a putative α-helix structure of 14 amino acids (Gag residues 311-324) and lies directly C-terminal to the capsid major homology region. We found that a deletion mutation in the α-helix drastically reduces virus particle production. Alanine-scanning mutagenetic analysis indicated that substitution mutations at residues Q311, V313, K314, W316, and M317 all impair virus particle production markedly. Membrane flotation assays suggested that some mutations in the dimer interface have slight effects on the efficient binding of Gag to membranes. Indirect immunofluorescence studies revealed that mutants defective in virus production exhibit a subcellular distribution pattern similar to that of wild-type. However, velocity sedimentation analysis showed that mutations significantly impairing virus particle production were also detrimental to Gag multimerization, suggesting that the impaired virus production may be due to a defect in Gag multimerization. These results support the proposal that residues in the capsid dimer interface play a crucial role in promoting Gag multimerization, possibly by facilitating stable Gag-Gag interactions.
- 中文關鍵字: --
- 英文關鍵字: Gag, HIV-1, major homology region, virus assembly