The structural biology of HIV-1: mechanistic and therapeutic insights.
Alan Engelman,Peter Cherepanov +1 more
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TLDR
Recent advances in HIV-1 structural biology are reviewed, focusing on the molecular mechanisms of viral replication and on the development of new therapeutics.Abstract:
Three-dimensional molecular structures can provide detailed information on biological mechanisms and, for cases in which the molecular function affects human health, can significantly aid in the development of therapeutic interventions. For almost 25 years, key components of the lentivirus HIV-1, including the envelope glycoproteins, the capsid and the replication enzymes reverse transcriptase, integrase and protease, have been scrutinized to near atomic-scale resolution. Moreover, structural analyses of the interactions between viral and host cell components have yielded key insights into the mechanisms of viral entry, chromosomal integration, transcription and egress from cells. 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.read more
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Molecular Recognition in Chemical and Biological Systems
TL;DR: Thermodynamic profiling, combined with X-ray structural and computational studies, is the key to elucidate the energetics of the replacement of water by ligands.
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APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages
Shraddha Sharma,Santosh K. Patnaik,R. Thomas Taggart,Eric Kannisto,Sally M. Enriquez,Paul Gollnick,Bora E. Baysal +6 more
TL;DR: It is shown that transcripts of hundreds of genes undergo site-specific C>U RNA editing in macrophages during M1 polarization and in monocytes in response to hypoxia and interferons.
Journal ArticleDOI
HIV Gag polyprotein: processing and early viral particle assembly
Neil M. Bell,Andrew M. L. Lever +1 more
TL;DR: This work has shown that the Gag polyprotein, the main structural protein of HIV-1 and all other retroviruses, has the ability to specifically recognize genomic RNA and both viral and host proteins as it traffics to the cell membrane.
Journal ArticleDOI
Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation.
Kellie A. Jurado,Hao Wang,Alison Slaughter,Lei Feng,Jacques J. Kessl,Yasuhiro Koh,Weifeng Wang,Allison Ballandras-Colas,Pratiq A. Patel,James R. Fuchs,Mamuka Kvaratskhelia,Alan Engelman +11 more
TL;DR: It is demonstrated that ALLinI potency is unexpectedly accounted for during the late phase of HIV-1 replication, and cooperative multimerization of IN by ALLINIs together with the inability for LEDGF/p75 to effectively engage the virus during its egress from cells underscores the multimodal mechanism of ALLINI action.
Journal ArticleDOI
An integrated map of HIV genome-wide variation from a population perspective
Guangdi Li,Guangdi Li,Supinya Piampongsant,Nuno R. Faria,Arnout Voet,Andrea-Clemencia Pineda-Peña,Andrea-Clemencia Pineda-Peña,Ricardo Khouri,Ricardo Khouri,Philippe Lemey,Anne-Mieke Vandamme,Anne-Mieke Vandamme,Kristof Theys +12 more
TL;DR: It is suggested that, in addition to the impact of protein multimerization and immune selective pressure on HIV-1 diversity, HIV-human protein interactions are facilitated by high variability within intrinsically disordered structures.
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
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TL;DR: The structure reveals a cavity-laden CD4–gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion.
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TL;DR: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer.
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