An Inhibitory Monoclonal Antibody Binds at the Turn of the Helix-Turn-Helix Motif in the N-terminal Domain of HIV-1 Integrase

Yi, Jizu; Arthur, Jonathan W.; Dunbrack, Roland L.; Skalka, Anna Marie

doi:10.1074/jbc.m005499200

Cited by 26 publications

(37 citation statements)

References 53 publications

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“…These insertions retained disintegration but had barely detectable levels of integration. Relevant to our mutants, it has been shown that a monoclonal antibody which interacts with amino acids 27 to 29 destabilizes the N-terminal helical bundle and decreases 3Ј processing and transfer activities of HIV-1 IN in vitro (95). In addition, it is known that deletion of the N-terminal 39 aa abolishes integration activity (25).…”

Section: Discussionmentioning

confidence: 69%

Revealing Domain Structure through Linker-Scanning Analysis of the Murine Leukemia Virus (MuLV) RNase H and MuLV and Human Immunodeficiency Virus Type 1 Integrase Proteins

Puglia¹,

Wang

Smith-Snyder³

et al. 2006

J Virol

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Methods have been developed for the comprehensive analysis of a gene by construction of a saturating or near-saturating library of mutants (5,78,83). This approach has defined domain boundaries, provided functional maps, and given insights into previously predicted unstructured loops (4,5,50,71,73,78,83). In this report, this method of insertional functional mapping is applied to three catalytically related domains: the Moloney murine leukemia virus (M-MuLV) RNase H domain of the reverse transcriptase (RT), and the M-MuLV and human immunodeficiency virus type 1 (HIV-1) integrase (IN) proteins. Inclusion of the HIV-1 IN protein assisted comparison and model building, since structural information is available (7,18,26,34,35,37,87). In the retroviral life cycle, the RNase H activity is required for viral replication during the conversion of the viral RNA (vRNA) into double-stranded DNA through the RNA-DNA intermediate. The IN protein is required for the insertion of the double-stranded DNA into the host chromosome, establishing the integrated provirus.The replication and integration of retroviral particles are two distinct yet interrelated processes. Replicative complexes and preintegrative complexes have been purified and characterized from infected cells (6, 9, 17, 28-30, 39, 52, 53, 55, 56, 66, 67). Within viral species as well as between viral species, the composition of replicative complexes differs from that of preintegrative complexes. Interactions between RT and IN are also reported (40,69,89,90,96), and multiple mutations of IN are known to alter viral replication (27,(58)(59)(60). Despite extensive efforts, the assembly of these complexes is not well understood. These studies have been assisted by structural studies. A structure of the M-MuLV RT has recently been reported (21), as have structures of related retroviral IN subdomains (8,14,18,19,26,35,43,87,94). However, to date, neither a structure of a complete retroviral IN protein nor one of a subdomain in complex with DNA has been obtained.The ability of retroviral particles to stably integrate into the host genome is a great benefit for gene delivery, but the potential for insertional mutagenesis cannot be overlooked (15,22,38,63). Schemes to target integration into alternative positions within the host chromosome to avoid this issue frequently involve generation of fusion proteins with novel targeting domains (10,48,84). The linker insertion genetic footprint provides a means to identify nonessential regions

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Section: Discussionmentioning

confidence: 69%

Revealing Domain Structure through Linker-Scanning Analysis of the Murine Leukemia Virus (MuLV) RNase H and MuLV and Human Immunodeficiency Virus Type 1 Integrase Proteins

Puglia¹,

Wang

Smith-Snyder³

et al. 2006

J Virol

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show abstract

“…1A). Details of the binding of the N-terminal domain to the inhibitory mAb17 have been reported (21); its epitope was mapped to a relatively neutral surface of the dimeric N-terminal domain, likely to be involved in protein-protein interaction. Here, we describe detailed binding studies and structural analyses of the interaction of the C-terminal domain-specific mAb33.…”

Section: Integrase (In)mentioning

confidence: 99%

“…For NMR experiments, the protein expression vectors pET28b/IN-(220 -270) and pET28b/IN-(220 -288) were prepared by inserting sequences encoding amino acids 220 -270 and 220 -288 of HIV-1 IN, respectively, into plasmid pET28b (Novagen, Madison, WI) as described (21). The products include four expression plasmid-encoded amino acids (GSHM) at their N termini, which remain after thrombin cleavage to remove the His 6 tag.…”

Section: Hiv-1 In Proteins and Anti-in Monoclonalmentioning

confidence: 99%

Mapping the Epitope of an Inhibitory Monoclonal Antibody to the C-terminal DNA-binding Domain of HIV-1 Integrase

Yi¹,

Cheng

Andrake

et al. 2002

Journal of Biological Chemistry

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“…The peptides found in the P1-P4 fractions were digested with trypsin under standard conditions for MALDI analysis, and the hydrolyzates were studied. Seven antigenic determinants (AGDs) have been reported for HIV IN corresponding to amino acid residues 5-22 (AGD1), 14-35 (AGD2) (Yi et al, 2000), 58-141 (AGD3), 141-172 (AGD4), 248-264 (AGD5) (Bizub-Bender et al, 1994), 208-228 (AGD6), and 251-271(AGD7) (Nilsen et al, 1996) (underlined in Fig. 14).…”

Section: Effect Of Dna On the Integrase Hydrolysis By Different Protementioning

confidence: 99%

Natural Catalytic Antibodies in Norm and in HIV-Infected Patients

Nevinsky¹

2011

Understanding HIV/AIDS Management and Care - Pandemic Approaches in the 21st Century

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An Inhibitory Monoclonal Antibody Binds at the Turn of the Helix-Turn-Helix Motif in the N-terminal Domain of HIV-1 Integrase

Cited by 26 publications

References 53 publications

Revealing Domain Structure through Linker-Scanning Analysis of the Murine Leukemia Virus (MuLV) RNase H and MuLV and Human Immunodeficiency Virus Type 1 Integrase Proteins

Revealing Domain Structure through Linker-Scanning Analysis of the Murine Leukemia Virus (MuLV) RNase H and MuLV and Human Immunodeficiency Virus Type 1 Integrase Proteins

Mapping the Epitope of an Inhibitory Monoclonal Antibody to the C-terminal DNA-binding Domain of HIV-1 Integrase

Natural Catalytic Antibodies in Norm and in HIV-Infected Patients

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