Activating region of HIV-1 Tat protein: vacuum UV circular dichroism and energy minimization

Tat protein is a trans-acting transcriptional activator of the human immunodeficiency virus type 1 and is essential for viral transcription. By homology with other transcriptional activators, Tat is expected to possess a nucleic acid binding region and a separate adjacent activating region. In order...

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Bibliographic Details
Published in:Biochemistry (Easton) 1991-06, Vol.30 (24), p.6013-6023
Main Authors: Loret, Erwann P, Vives, Eric, Ho, Pui Shing, Rochat, Herve, Van Rietschoten, Jurphaas, Johnson, W. Curtis
Format: Article
Language:English
Subjects:
AIDS/HIV
Amino Acid Sequence
Biological and medical sciences
Circular Dichroism
Computer Simulation
Fundamental and applied biological sciences. Psychology
Gene Products, tat - chemical synthesis
Gene Products, tat - chemistry
HIV-1 - genetics
human immunodeficiency virus 1
Hydrogen Bonding
Microbiology
Models, Molecular
Molecular Sequence Data
Peptides - chemical synthesis
Peptides - chemistry
Protein Conformation
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
Spectrophotometry, Ultraviolet
tat Gene Products, Human Immunodeficiency Virus
Virology
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Summary:Tat protein is a trans-acting transcriptional activator of the human immunodeficiency virus type 1 and is essential for viral transcription. By homology with other transcriptional activators, Tat is expected to possess a nucleic acid binding region and a separate adjacent activating region. In order to localize the activating region of Tat, we have synthesized the sequences 2-23 and 38-60 of the protein. These two peptides contain the two candidates for the activating regions proposed from mutation experiments in previous studies: sequence 1-13 and sequence 38-45. The argument advanced to justify the location of the activating region within the sequence 1-13 was the periodicity of acidic, polar, and hydrophobic residues consistent with that of an amphipathic alpha-helix, similar to the activating region of many eukaryotic transcriptional activators. We have monitored by vacuum UV circular dichroism the ability of each peptide to adopt an alpha-helical conformation under conditions that strongly favor the formation of secondary structures. Only peptide 38-60 adopts an alpha-helical conformation in these conditions, in keeping with Chou-Fasman prediction. Energy minimization and molecular dynamics were carried out for several possible conformations of sequences 1-14 and 38-60. Our results indicate that only the sequence 38-45 is able to form an alpha-helix with amphipathic characteristics.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00238a027