First large scale chemical synthesis of the 72 amino acid HIV-1 nucleocapsid protein NCp7 in an active form.
The nucleocapsid protein (NC) of the human immunodeficiency virus type 1 plays a crucial role in the formation of infectious viral particles and therefore should be a major target for the development of antiviral agents. This requires an investigation of NC protein structure and of its interactions with both primer tRNA(Lys,3) and genomic RNA. Nucleocapsid protein NCp7, which results from the maturation of NCp15, contains two zinc fingers flanked by sequences rich in basic and proline residues. Here we report the first synthesis of large quantities of NCp7 able to activate HIV-1 RNA dimerization and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. In addition UV spectroscopic analyses performed to characterize the Co2+ binding properties of each zinc finger suggest that the two fingers probably interact in NCp7.
de Rocquigny
H
H
Département de Chimie Organique, U266 INSERM-UA498 CNRS UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Ficheux
D
D
Gabus
C
C
Fournié-Zaluski
M C
MC
Darlix
J L
JL
Roques
B P
BP
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002213:Capsid / Q000138:chemical synthesis* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D011485:Protein Binding; D011487:Protein Conformation; D012357:RNA, Transfer, Lys / Q000378:metabolism; D014758:Viral Core Proteins / Q000138:chemical synthesis* / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
D010455:Peptides; D012357:RNA, Transfer, Lys; D014758:Viral Core Proteins; D002118:Calcium