ArticleThe Journal of biological chemistry2012
Context surrounding processing sites is crucial in determining cleavage rate of a subset of processing sites in HIV-1 Gag and Gag-Pro-Pol polyprotein precursors by viral protease.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Real-Time Imaging of HIV-1 Protease Activation and Substrate Cleavage in Single Virions Assembling on the Plasma Membrane.Viruses · 2026Article
- High-throughput screening and characterization of novel inhibitors targeting HIV-1 protease precursor autoprocessing.Scientific reports · 2025Article
- Mechanism and Kinetics of HIV-1 Protease Activation.Viruses · 2024Review
- Neutral sphingomyelinase 2 is required for HIV-1 maturation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Sequence dependencies and biophysical features both govern cleavage of diverse cut-sites by HIV protease.Protein science : a publication of the Protein Society · 2022Article
- Structural maturation of the HIV-1 RNA 5' untranslated region by Pr55RNA biology · 2022Article
- A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors.Retrovirology · 2021Article
- Immature HIV-1 assembles from Gag dimers leaving partial hexamers at lattice edges as potential substrates for proteolytic maturation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Picomolar to Micromolar: Elucidating the Role of Distal Mutations in HIV-1 Protease in Conferring Drug Resistance.ACS chemical biology · 2019Article
- Dominant Negative MA-CA Fusion Protein Is Incorporated into HIV-1 Cores and Inhibits Nuclear Entry of Viral Preintegration Complexes.Journal of virology · 2019Article
- Article
- Targeting HIV-1 Protease Autoprocessing for High-throughput Drug Discovery and Drug Resistance Assessment.Scientific reports · 2019Article
- HIV-1 Protease Uses Bi-Specific S2/S2' Subsites to Optimize Cleavage of Two Classes of Target Sites.Journal of molecular biology · 2018Article
- Insights into the activity of maturation inhibitor PF-46396 on HIV-1 clade C.Scientific reports · 2017Article
- Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity.Antimicrobial agents and chemotherapy · 2016Article
- HIV-1 protease cleaves the serine-threonine kinases RIPK1 and RIPK2.Retrovirology · 2015Article
- A Direct Interaction with RNA Dramatically Enhances the Catalytic Activity of the HIV-1 Protease In Vitro.Journal of molecular biology · 2015Article
- Deep sequencing of protease inhibitor resistant HIV patient isolates reveals patterns of correlated mutations in Gag and protease.PLoS computational biology · 2015Article
- A new ensemble coevolution system for detecting HIV-1 protein coevolution.Biology direct · 2015Article
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6 authors.
Funding
Abstract
Processing of the human immunodeficiency virus type 1 (HIV-1) Gag and Gag-Pro-Pol polyproteins by the HIV-1 protease (PR) is essential for the production of infectious particles. However, the determinants governing the rates of processing of these substrates are not clearly understood. We studied the effect of substrate context on processing by utilizing a novel protease assay in which a substrate containing HIV-1 matrix (MA) and the N-terminal domain of capsid (CA) is labeled with a FlAsH (fluorescein arsenical hairpin) reagent. When the seven cleavage sites within the Gag and Gag-Pro-Pol polyproteins were placed at the MA/CA site, the rates of cleavage changed dramatically compared with that of the cognate sites in the natural context reported previously. The rate of processing was affected the most for three sites: CA/spacer peptide 1 (SP1) (≈10-fold increase), SP1/nucleocapsid (NC) (≈10-30-fold decrease), and SP2/p6 (≈30-fold decrease). One of two multidrug-resistant (MDR) PR variants altered the pattern of processing rates significantly. Cleavage sites within the Pro-Pol region were cleaved in a context-independent manner, suggesting for these sites that the sequence itself was the determinant of rate. In addition, a chimera consisting of SP1/NC P4-P1 and MA/CA P1'-P4' residues (ATIM↓PIVQ) abolished processing by wild type and MDR proteases, and the reciprocal chimera consisting of MA/CA P4-P1 and SP1/NC P1'-4' (SQNY↓IQKG) was cleaved only by one of the MDR proteases. These results suggest that complex substrate interactions both beyond the active site of the enzyme and across the scissile bond contribute to defining the rate of processing by the HIV-1 PR.
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