Browsing by Author "Engelman, Alan"
Now showing items 1-20 of 28
-
Architecture and Regulation of the Arenavirus Polymerase Complex
Kranzusch, Philip (2013-02-15)Viruses are the only organisms known to store their genetic information solely in the form of RNA, and have thus evolved unique machinery to replicate an RNA genome and initiate viral gene expression in the infected cell. ... -
Biochemical Characterization of Novel Retroviral Integrase Proteins
Ballandras-Colas, Allison; Naraharisetty, Hema; Li, Xiang; Serrao, Erik; Engelman, Alan (Public Library of Science, 2013)Integrase is an essential retroviral enzyme, catalyzing the stable integration of reverse transcribed DNA into cellular DNA. Several aspects of the integration mechanism, including the length of host DNA sequence duplication ... -
Chromatinized Templates Reveal the Requirement for the LEDGF/p75 PWWP Domain During HIV-1 Integration in vitro
Botbol, Yaïr; Raghavendra, Nidhanapati K.; Rahman, Shaila; Engelman, Alan N.; Lavigne, Marc (Oxford University Press, 2008)Integration is an essential step in the retroviral lifecycle, and the lentiviral integrase binding protein lens epithelium-derived growth factor (LEDGF)/p75 plays a crucial role during human immunodeficiency virus type 1 ... -
CPSF6 LICENSES HIV-1 INTEGRATION INTO POL II-PAUSED GENES REGULATED by P-TEFb and U2 snRNP
Singh, Parmit; Annamalai, Arun; Kvaratskhelia, Mamuka; Engelman, Alan (2023-05)Pre-mRNA splicing regulates promoter-proximal Pol II pausing and alternative polyadenylation (APA). Splicing inhibitors increase pausing and use of proximal polyadenylation sites (PAS) for comparatively long (>4 introns) ... -
Cryo-EM reveals a novel octameric integrase structure for β-retroviral intasome function
Ballandras-Colas, Allison; Brown, Monica; Cook, Nicola J.; Dewdney, Tamaria G.; Demeler, Borries; Cherepanov, Peter; Lyumkis, Dmitry; Engelman, Alan N. (2016)Retroviral integrase (IN) catalyzes the integration of viral DNA (vDNA) into host target (tDNA), which is an essential step in the lifecycle of all retroviruses1. Prior structural characterization of IN-vDNA complexes, or ... -
Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice
Wang, Hao; Shun, Ming-Chieh; Dickson, Amy K.; Engelman, Alan N. (Public Library of Science, 2015)Hepatoma-derived growth factor (HDGF) related protein 2 (HRP2) and lens epithelium-derived growth factor (LEDGF)/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human ... -
Engineered Hyperactive Integrase for Concerted HIV-1 DNA Integration
Li, Min; Jurado, Kellie A.; Lin, Shiqiang; Engelman, Alan; Craigie, Robert (Public Library of Science, 2014)The DNA cutting and joining reactions of HIV-1 integration are catalyzed by integrase (IN), a viral protein that functions as a tetramer bridging the two viral DNA ends (intasome). Two major obstacles for biochemical and ... -
Foreign DNA capture during CRISPR–Cas adaptive immunity
Nuñez, James K.; Harrington, Lucas B.; Kranzusch, Philip J.; Engelman, Alan N.; Doudna, Jennifer A. (2015)Bacteria and archaea generate adaptive immunity against phages and plasmids by integrating foreign DNA of specific 30–40 base pair (bp) lengths into clustered regularly interspaced short palindromic repeats (CRISPR) loci ... -
The functional interplay between TNPO3, CPSF6 and HIV-1 CA
Oztop, Ilker (2014-10-21)Lentiviruses can infect postmitotic cells, indicative of a role for the nucleocytoplasmic transport machinery. Genome-wide RNA interference screens identified transportin 3 (TNPO3) that may regulate human immunodeficiency ... -
HIV-1 capsid engages nucleoporin NUP153 to promote viral nuclear entry
Matreyek, Kenneth Anzai (2014-02-25)Lentiviruses can infect non-dividing cells, and various cellular nuclear transport proteins provide crucial functions for lentiviral nuclear entry and integration. Genome-wide small interfering RNA screens previously ... -
HIV-1 Integration Favors Genes Associated With Promoter-Proximal Pol II Pausing
Singh, Parmit; Annamalai, Arun; Kvaratkshelia, Mamuka; Engelman, Alan (2021-05)HIV-1 integration targeting is mediated by interactions of viral integrase and capsid with LEDGF/p75 and CPSF6, respectively. HIV-1 also prefers to integrate into highly spliced genes, but the role of pre-mRNA splicing in ... -
HIV-1 Preferentially Targets Genes Regulated by PAF-1 and U2 snRNP for Integration
Singh, Parmit; Annamalai, Arun; Kvaratkshelia, Mamuka; Engelman, Alan (2023-08-04)Pre-mRNA splicing is coupled with promoter-proximal Pol II pausing and alternative polyadenylation (APA). Splicing inhibitors increase pausing and the use of proximal polyadenylation sites (PAS) in intron rich genes by ... -
Host and viral determinants for MxB restriction of HIV-1 infection
Matreyek, Kenneth A; Wang, Weifeng; Serrao, Erik; Singh, Parmit Kumar; Levin, Henry L; Engelman, Alan (BioMed Central, 2014)Background: Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite ... -
HRP2 Determines the Efficiency and Specificity of HIV-1 Integration in LEDGF/p75 Knockout Cells but Does Not Contribute to the Antiviral Activity of a Potent LEDGF/p75-Binding Site Integrase Inhibitor
Wang, Hao; Jurado, Kellie Ann; Wu, Xiaolin; Shun, Ming-Chieh; Li, Xiang; Ferris, Andrea L.; Smith, Steven J.; Patel, Pratiq A.; Fuchs, James R.; Cherepanov, Peter; Kvaratskhelia, Mamuka; Hughes, Stephen H.; Engelman, Alan N. (Oxford University Press, 2012)The binding of integrase (IN) to lens epithelium-derived growth factor (LEDGF)/p75 in large part determines the efficiency and specificity of HIV-1 integration. However, a significant residual preference for integration ... -
Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding
Serrao, Erik; Krishnan, Lavanya; Shun, Ming-Chieh; Li, Xiang; Cherepanov, Peter; Engelman, Alan; Maertens, Goedele N. (Oxford University Press, 2014)Retroviruses favor target-DNA (tDNA) distortion and particular bases at sites of integration, but the mechanism underlying HIV-1 selectivity is unknown. Crystal structures revealed a network of prototype foamy virus (PFV) ... -
Integrase-mediated spacer acquisition during CRISPR–Cas adaptive immunity
Nuñez, James K.; Lee, Amy S.Y.; Engelman, Alan; Doudna, Jennifer A. (2015)Bacteria and archaea insert spacer sequences acquired from foreign DNAs into CRISPR loci to generate immunological memory. The Escherichia coli Cas1–Cas2 complex mediates spacer acquisition in vivo, but the molecular ... -
LEDGF/P75 DIRECTS HIV-1 TO INTEGRATE INTO HIGHLY SPLICED GENES DESPITE THEIR COMPARATIVELY LOW EXPRESSION
Singh, Parmit; Engelman, AlanIntegration of HIV-1 into genes depends on multiple factors including transcription, splicing, LEDGF/p75, and CPSF6. But, the precise role of mRNA splicing in HIV-1 integration targeting is unclear. Transcriptional intron ... -
LEDGF/p75-dependent HIV-1 integration targeting into spliced genes: A role for the DNA damage response
Singh, Parmit; Engelman, Alan (2020-04)HIV-1 integration site selection is regulated at the level of transcription, splicing, histone modifications, super enhancer, nuclear architecture, and interactions of viral proteins with host factors. However, the mechanism ... -
The Lentiviral Integrase Binding Protein LEDGF/p75 and HIV-1 Replication
Engelman, Alan N.; Cherepanov, Peter (Public Library of Science, 2008)Retroviral replication proceeds through a stable proviral DNA intermediate, and numerous host cell factors have been implicated in its formation. In particular, recent results have highlighted an important role for the ... -
The mechanism of H171T resistance reveals the importance of Nδ-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase
Slaughter, Alison; Jurado, Kellie A; Deng, Nanjie; Feng, Lei; Kessl, Jacques J; Shkriabai, Nikoloz; Larue, Ross C; Fadel, Hind J; Patel, Pratiq A; Jena, Nivedita; Fuchs, James R; Poeschla, Eric; Levy, Ronald M; Engelman, Alan; Kvaratskhelia, Mamuka (BioMed Central, 2014)Background: Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are an important new class of anti-HIV-1 agents. ALLINIs bind at the IN catalytic core domain (CCD) dimer interface occupying the principal binding pocket ...