Research Topics
Genomes and Genes | ALAN N ENGELMANSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Publications
The roles of cellular factors in retroviral integrationA Engelman
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
Curr Top Microbiol Immunol 281:209-38. 2003..The potential to interfere with proper integration by blocking either integrase catalysis or the function of cellular integration cofactors is also discussed...
The structural biology of HIV-1: mechanistic and therapeutic insightsAlan Engelman
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA
Nat Rev Microbiol 10:279-90. 2012..Here, we review recent advances in HIV-1 structural biology, focusing on the molecular mechanisms of viral replication and on the development of new therapeutics...
Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virusXiang Li
Address correspondence to Alan Engelman
J Virol 86:3861-79. 2012....
Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integraseMohd J Dar
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA, USA
Retrovirology 6:94. 2009..The F185K core domain mutation, which increases integrase protein solubility, was furthermore analyzed in a subset of mutants...
The ups and downs of gene expression and retroviral DNA integrationAlan Engelman
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 102:1275-6. 2005
The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replicationAlan Engelman
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA
PLoS Pathog 4:e1000046. 2008....
Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75Peter Cherepanov
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 102:17308-13. 2005....
Quantitative analysis of HIV-1 preintegration complexesAlan Engelman
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute and Division of AIDS, Harvard Medical School, 44 Binney Street, CLSB 1010, Boston, MA 02115, USA
Methods 47:283-90. 2009..This study details HIV-1 infection, PIC extraction, partial purification, and quantitative analyses of integrase 3' processing and DNA strand transfer activities...
AIDS/HIV. A reversal of fortune in HIV-1 integrationAlan Engelman
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA
Science 316:1855-7. 2007
Biochemical and genetic analyses of integrase-interacting proteins lens epithelium-derived growth factor (LEDGF)/p75 and hepatoma-derived growth factor related protein 2 (HRP2) in preintegration complex function and HIV-1 replicationNick Vandegraaff
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
Virology 346:415-26. 2006..We conclude that cells knocked-out for LEDGF/p75 and/or HRP2 will be useful genetic tools to address the roles of these host cell factors in HIV-1 replication...
Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a strict correlation between in vitro protein binding and HIV-1 fitnessShaila Rahman
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
Virology 357:79-90. 2007..Thus, the relative affinity of the in vitro IN-LEDGF/p75 interaction is not a universal predictor of IN mutant viral fitness...
Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear importAna Limon
Department of Pathology, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
J Virol 76:10598-607. 2002....
Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivityMing Chieh Shun
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute and Division of AIDS, Harvard Medical School, Boston, MA 02115, USA
J Virol 82:11555-67. 2008..This initial systematic mutagenesis of a PWWP domain identifies amino acid residues critical for chromatin binding function and the consequences of their changes on HIV-1 integration and infection...
Identification of host proteins required for HIV infection through a functional genomic screenAbraham L Brass
Department of Genetics, Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Science 319:921-6. 2008..This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy...
The requirement for cellular transportin 3 (TNPO3 or TRN-SR2) during infection maps to human immunodeficiency virus type 1 capsid and not integraseLavanya Krishnan
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
J Virol 84:397-406. 2010..We therefore conclude that capsid, not integrase, is the dominant viral factor that dictates transportin 3 dependency during HIV-1 infection...
LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integrationMing Chieh Shun
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA
Genes Dev 21:1767-78. 2007..Akin to yeast retrotransposons, disrupting the lentiviral targeting mechanism significantly perturbs overall integration...
LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: implications for the mechanism of viral cDNA integrationNidhanapati K Raghavendra
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
Virology 360:1-5. 2007..We therefore speculate that LEDGF/p75 function is restricted to a point in the viral lifecycle that occurs after the formation of the preintegration synaptic complex, for example, as a chromatin-associated tethering factor...
Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrasePeter Cherepanov
Departments of Cancer Immunology and AIDS and Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
J Biol Chem 279:48883-92. 2004..LEDGF/p75 and HRP2 are predicted to share a similar domain organization and have an evident evolutionary and likely functional relationship...
Human cell proteins and human immunodeficiency virus DNA integrationFanny Turlure
Department of Pathology, Harvard Medical School, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Front Biosci 9:3187-208. 2004..We also present experimental results of human cell proteins that coimmunoprecipitated with HIV-1 IN following its expression in HeLa cells and discuss these results in light of the previously-identified integration cofactors...
Transcriptional co-activator p75 binds and tethers the Myc-interacting protein JPO2 to chromatinGoedele N Maertens
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
J Cell Sci 119:2563-71. 2006..Our results suggest a role for p75 in the Myc regulatory network, and indicate that p75 is a general adaptor protein tethering divergent factors to chromatin through its versatile integrase-binding domain...
The SET complex acts as a barrier to autointegration of HIV-1Nan Yan
Department of Pediatrics, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS Pathog 5:e1000327. 2009..Therefore, the SET complex facilitates HIV-1 infection by preventing suicidal autointegration...
Simian virus 40-based replication of catalytically inactive human immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and monocyte-derived macrophagesRichard Lu
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts 02115, USA
J Virol 78:658-68. 2004..SV40-based HIV-1 integrase mutant replication in otherwise nonpermissive cells suggests alternative approaches to standard integrase-mediated retroviral gene transfer strategies...
Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replicationRichard Lu
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
J Virol 78:12735-46. 2004..Since HIV-1(C130A) grew like the wild type, we conclude that Cys-130 is not essential for replication and speculate that perturbation of integrase structure contributed to the pleiotropic HIV-1(C130G) phenotype...
Wild-type levels of nuclear localization and human immunodeficiency virus type 1 replication in the absence of the central DNA flapAna Limon
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Virol 76:12078-86. 2002..Our results indicate that the central DNA flap does not play a major role in either preintegration complex nuclear import or HIV-1 replication in a variety of cell types...
The barrier-to-autointegration factor is a component of functional human immunodeficiency virus type 1 preintegration complexesChou Wen Lin
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
J Virol 77:5030-6. 2003..These data are consistent with the model that BAF functions as an integration cofactor in vivo...
Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75Goedele Maertens
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
J Biol Chem 279:33421-9. 2004..Moreover, a single amino acid change in the NLS was sufficient to exclude the mutant LEDGF/p75 protein from the nucleus and abolish nuclear import of HIV-1 integrase...
Genetic analyses of conserved residues in the carboxyl-terminal domain of human immunodeficiency virus type 1 integraseRichard Lu
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
J Virol 79:10356-68. 2005....
Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75Peter Cherepanov
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
Nat Struct Mol Biol 12:526-32. 2005..The initial structure determination of a host cell factor that tightly binds to a retroviral enzyme lays the groundwork for understanding enzyme-host interactions important for viral replication...
Intracellular transport of human immunodeficiency virus type 1 integraseEric Devroe
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
J Cell Sci 116:4401-8. 2003..These results provide new insight into human immunodeficiency virus type 1 integrase intracellular dynamics...
Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1Felipe Diaz-Griffero
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
Virology 351:404-19. 2006....
Genetic analyses of DNA-binding mutants in the catalytic core domain of human immunodeficiency virus type 1 integraseRichard Lu
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney St. Boston, MA 02115, USA
J Virol 79:2493-505. 2005..The results of these analyses highlight conserved CCD residues that are important for HIV-1 replication and integration and define the relationship between DNA binding and catalysis that occurs during integration in vivo...
Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replicationRichard Lu
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
J Virol 79:12584-91. 2005..We therefore concluded that mutations like K34A disrupted higher-order interactions important for PIC function/maturation compared to the innate catalytic activity of IN enzyme...
A tripartite DNA-binding element, comprised of the nuclear localization signal and two AT-hook motifs, mediates the association of LEDGF/p75 with chromatin in vivoFanny Turlure
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
Nucleic Acids Res 34:1653-65. 2006....
HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinasesEric Devroe
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
Virology 331:181-9. 2005..These studies identify two new virion-associated host cell enzymes and suggest a novel mechanism by which HIV-1 alters the intracellular environment of human cells...
Structure-based modeling of the functional HIV-1 intasome and its inhibitionLavanya Krishnan
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 107:15910-5. 2010..Our findings highlight the structural basis for HIV-1 integration and define the mechanism of its inhibition, which should help in formulating new drugs to inhibit viruses resistant to first-in-class compounds...
Isolation and analysis of HIV-1 preintegration complexesAlan Engelman
Department of Cancer Immunology, Dana Farber Cancer Institute and Division of AIDS, Harvard Medical School, Boston, MA, USA
Methods Mol Biol 485:135-49. 2009..This chapter describes techniques for isolating HIV-1 PICs from cells as well as quantifying their level of integration activity in vitro...
Differential sensitivities of retroviruses to integrase strand transfer inhibitorsYasuhiro Koh
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, CLS 1010, Boston, MA 02115, USA
J Virol 85:3677-82. 2011..The drugs intermediately inhibited intracisternal A-particle retrotransposition but were inactive against Sleeping Beauty transposition and long interspersed nucleotide element 1 (LINE-1) retrotransposition...
The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsidKenneth A Matreyek
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 450 Brookline Avenue, CLS 1010, Boston, MA 02215, USA
J Virol 85:7818-27. 2011..These results suggest that capsid, likely by the qualities of its uncoating, determines whether HIV-1 requires cellular NUP153 for PIC nuclear import...
Identification and characterization of persistent intracellular human immunodeficiency virus type 1 integrase strand transfer inhibitor activityYasuhiro Koh
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA
Antimicrob Agents Chemother 55:42-9. 2011..Combined intracellular persistence and virucidal activities suggest potential pre-exposure prophylaxis applications for EVG...
Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infectionZhihai Si
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 103:7454-9. 2006..Particular features of this subset of cytoplasmic TRIM proteins may be conducive to the convergent evolution of virus-restricting factors...
General guidelines for experimenting with HIVKaren B Byers
Dana Farber Cancer Institute, Boston, Massachusetts, USA
Curr Protoc Immunol . 2004..The first protocol in this unit establishes a general framework for working safely with HIV and the second describes the proper storage of HIV stocks and test supernatants...
Wild-type levels of human immunodeficiency virus type 1 infectivity in the absence of cellular emerin proteinMing Chieh Shun
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
J Virol 81:166-72. 2007....
Research Grants
- Nuclear Localization of HIV-1 Preintegration ComplexesAlan Engelman; Fiscal Year: 2006..abstract_text> ..
- HIV-1 Integrase Structural BiologyAlan Engelman; Fiscal Year: 2007....
- HIV-1 Preintegration Trafficking and Nuclear LocalizationAlan Engelman; Fiscal Year: 2007..This knowledge in the long run will define novel targets for therapeutic interaction to develop new anti-viral drugs in the fight against HIV/AIDS. ..
- BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATIONAlan Engelman; Fiscal Year: 2009..abstract_text> ..
- HIV-1 Preintegration Trafficking and Nuclear LocalizationALAN N ENGELMAN; Fiscal Year: 2010..This knowledge in the long run will define novel targets for therapeutic interaction to develop new anti-viral drugs in the fight against HIV/AIDS. ..
- HIV-1 Integrase Structural BiologyALAN N ENGELMAN; Fiscal Year: 2010..abstract_text> ..
- LEDGF-Integrase Structural BiologyAlan Engelman; Fiscal Year: 2005..abstract_text> ..
- BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATIONAlan Engelman; Fiscal Year: 1999..C. Examination of higher order protein-protein and protein-DNA interactions important for preintegration complex activity. D. Develop an assay for authentic integration of exogenous HIV-1 DNA. ..
- MECHANISM OF NON-INTEGRASE-MEDIATED HIV-1 REPLICATIONAlan Engelman; Fiscal Year: 2001..Further aims are to develop gene therapy vectors based on non-integrating retroviruses. ..
- Nuclear Localization of HIV-1 Preintegration ComplexesAlan Engelman; Fiscal Year: 2003..abstract_text> ..
- BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATIONAlan Engelman; Fiscal Year: 2004..The results of these experiments will be used to formulate a detailed model of the structural and functional organization of HIV-1 PICs, which will aid the design of antiviral drugs targeted against HIV-1 integration. ..
