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PMID: 9499062 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A putative alpha-helical structure which overlaps the capsid-p2 boundary in the human immunodeficiency virus type 1 Gag precursor is crucial for viral particle assembly.

Journal of virology ·Vol. 72 ·No. 3 ·1998-03-00 ·Pages 2072-8

Accola MA, Höglund S, Göttlinger HG

Abstract

The capsid (CA) and nucleocapsid domains of the human immunodeficiency virus type 1 Gag polyprotein are separated by the p2 spacer peptide, which is essential for virus replication. Previous studies have revealed that p2 has an important role in virus morphogenesis. In this paper, we show that a crucial assembly determinant maps to the highly conserved N terminus of p2, which is predicted to form part of an alpha-helix that begins in CA. A mutational analysis indicates that the ability of the N terminus of p2 to adopt an alpha-helical structure is essential for its function during virus assembly. To prevent CA-p2 processing, it was necessary to mutate both the CA-p2 cleavage site and an internal cleavage site within p2. Virions produced by the double mutant lacked a conical core shell and instead contained a thin electron-dense shell about 10 nm underneath the virion membrane. These results suggest that p2 is transiently required for proper assembly, but needs to be removed from the C terminus of CA to weaken CA-CA interactions and allow the rearrangement of the virion core shell during virus maturation.

MeSH Terms
Amino Acid Sequence Capsid Chromosome Mapping Conserved Sequence Gene Products, gag/chemistry,genetics,metabolism HIV-1/genetics,physiology,ultrastructure HeLa Cells Humans Jurkat Cells Molecular Sequence Data Mutagenesis Peptide Fragments/chemistry,genetics,metabolism Protein Conformation Protein Precursors/chemistry,genetics,metabolism Structure-Activity Relationship Virion/ultrastructure Virus Assembly gag Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, gag Peptide Fragments Protein Precursors gag Gene Products, Human Immunodeficiency Virus p2 gag peptide, Human immunodeficiency virus 1 p55 gag precursor protein, Human immunodeficiency virus 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Accola M A
Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Höglund S
Göttlinger H G
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.3.2072-2078.1998
Published
1998-03-00
Pages
2072-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC109501
Subset
IM
Grants
NIAID NIH HHS · R37 AI029873 · United States
NIAID NIH HHS · P30 AI028691 · United States
NIAID NIH HHS · AI29873 · United States
NCI NIH HHS · T32 CA009141 · United States
NIAID NIH HHS · AI28691 · United States
NCI NIH HHS · T32 CA09141 · United States
NIAID NIH HHS · R01 AI029873 · United States
NCI NIH HHS · P30 CA006516 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.3.2072-2078.1998 PMC Full Text View journal details
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