Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection
UMass Chan AffiliationsProgram in Gene Function and Expression
Program in Molecular Medicine
Graduate School of Biomedical Sciences
Graduate School of Biomedical Sciences
KeywordsBase Sequence; Binding Sites; Consensus Sequence; Directed Molecular Evolution; Gene Products, gag; Gene Products, pol; HIV Antigens; HIV-1; Molecular Sequence Data; Protein Binding; Protein Precursors; RNA, Viral; RNA-Binding Proteins; Sequence Homology, Nucleic Acid; T-Lymphocytes; *Viral Proteins; gag Gene Products, Human Immunodeficiency Virus
Medicine and Health Sciences
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AbstractThe human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a multifunctional structural protein synthesized as part of the Pr55 gag polyprotein. We have used in vitro genetic selection to identify an RNA consensus sequence that specifically interacts with MA (Kd = 5 x 10(-7) M). This 13-nt MA binding consensus sequence bears a high degree of homology (77%) to a region (nt 1433-1446) within the POL open reading frame of the HIV-1 genome (consensus sequence from 38 HIV-1 strains). Chemical interference experiments identified the nucleotides within the MA binding consensus sequence involved in direct contact with MA. We further demonstrate that this RNA-protein interaction is mediated through a stretch of basic amino acids within MA. Mutations that disrupt the interaction between MA and its RNA binding site within the HIV-1 genome resulted in a measurable decrease in viral replication.
RNA. 2001 Apr;7(4):576-84.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32436
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