Important changes in biochemical properties and function of mutated LLP12 domain of HIV-1 gp41.
The human immunodeficiency virus type 1 gp41 possesses an unusually long and conserved cytoplasmic region. Mutations in the LLP12 domain in this region have been shown to significantly affect viral competence. It is likely that the impaired infectivity of this mutated virus involves certain biochemical aspects of the peptide LLP12. To test our assumptions, some important biochemical properties and functions of LLP12 domain were studied. The recombinant peptide LLP12 (LLP12 domain on gp41, including LLP1 and LLP2 domains) was prepared via bacterial expression system. Biochemical analysis directly demonstrated its multimeric potential and membrane-binding ability. Several arginine residues in this domain were observed to be extremely highly conserved. Interestingly, the LLP12 mutants constructed by substitution of these arginine residues with alanine (separate mutations in LLP1 or LLP2 or both) showed apparent decreases in their multimeric potential and membrane-binding ability. Comparing our results with independent data on human immunodeficiency virus from other researchers, it appears that both the multimeric state and the membrane affinity of the LLP12 domain of human immunodeficiency virus type 1 gp41 could be involved in viral competence and in the mechanism of human immunodeficiency virus type 1 Env-mediated cell fusion.
Zhu
Yun
Y
Laboratory of Immunology, Department of Biology, Tsinghua University and Protein Science Laboratory of the Ministry of Education, Beijing 100084, China.
Lu
Lu
L
Chao
Lijun
L
Chen
Ying-Hua
YH
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D015700:HIV Envelope Protein gp41; D010455:Peptides; C514787:gp41 protein, Human immunodeficiency virus 1