Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection
Graduate School of Biomedical Sciences; Graduate School of Biomedical Sciences; Program in Molecular Medicine; Program in Gene Function and Expression
Medical Subject Headings
Base 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
Life Sciences | Medicine and Health Sciences
The 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.
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Citation: RNA. 2001 Apr;7(4):576-84.
Purohit, Aruna; Dupont, Stefan A.; Stevenson, Mario; and Green, Michael R., "Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection" (2001). GSBS Student Publications. Paper 1006.