Document 0595 DOCN M9550595 TI The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity. DT 9505 AU Ottmann M; Gabus C; Darlix JL; LaboRetro, Unite de Virologie Humaine, Ecole Normale; Superieure-Institut National de la Sante et de la Recherche; Medicale, Lyon, France. SO J Virol. 1995 Mar;69(3):1778-84. Unique Identifier : AIDSLINE MED/95156609 AB The nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is a 72-amino-acid peptide containing two CCHC-type zinc fingers linked by a short basic sequence, 29RAPRKKG35, which is conserved in HIV-1 and simian immunodeficiency virus. The complete three-dimensional structure of NCp7 has been determined by 1H-nuclear magnetic resonance spectroscopy (N. Morellet, H. de Rocquigny, Y. Mely, N. Jullian, H. Demene, M. Ottmann, D. Gerard, J. L. Darlix, M. C. Fournie-Zaluski, and B. P. Roques, J. Mol. Biol. 235:287-301, 1994) and revealed a central globular domain where the two zinc fingers are brought in close proximity by the RAPRKKG linker. To examine the role of this globular structure and more precisely of the RAPRKKG linker in virion structure and infectivity, we generated HIV-1 DNA mutants in the RAPRKK sequence of NCp7 and analyzed the mutant virions produced by transfected cells. Mutations that probably alter the structure of NCp7 structure led to the formation of very poorly infectious virus (A30P) or noninfectious virus (P31L and R32G). In addition, the P31L mutant did not contain detectable amounts of reverse transcriptase and had an immature core morphology, as determined by electron microscopy. On the other hand, mutations changing the basic nature of NCp7 had poor effect. R29S had a wild-type phenotype, and the replacement of 32RKK34 by SSS (S3 mutant) resulted in a decrease by no more than 100-fold of the virus titer. These results clearly show that the RAPRKKG linker contains residues that are critical for virion structure and infectivity. DE Amino Acid Sequence Animal Capsid/CHEMISTRY/*PHYSIOLOGY Cell Line Cercopithecus aethiops DNA Primers/CHEMISTRY Gene Products, gag/CHEMISTRY/*PHYSIOLOGY HIV-1/CHEMISTRY/PATHOGENICITY/*ULTRASTRUCTURE In Vitro Molecular Sequence Data Morphogenesis Mutagenesis, Site-Directed RNA, Viral/METABOLISM Structure-Activity Relationship Support, Non-U.S. Gov't Zinc Fingers JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).