Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics

Zhao, Gongpu; Perilla, Juan R.; Yufenyuy, Ernest L.; Meng, Xin; Chen, Bin; Ning, Jiying; Ahn, Jin-Woo; Gronenborn, Angela M.; Schulten, Klaus; Aiken, Christopher; Zhang, Peijun

doi:10.1038/nature12162

Cited by 745 publications

(1,027 citation statements)

References 28 publications

(48 reference statements)

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“…In that sense, our approach bears an analogy with the use of low-resolution Cryo-EM in combination with atomistic modeling to produce fully atomistic models of large structures (93), including chromatin components (94,95). Unlike Cryo-EM, our approach can be used at ambient conditions.…”

Section: Resultsmentioning

confidence: 99%

Partially Assembled Nucleosome Structures at Atomic Detail

Rychkov

Ilatovskiy

Nazarov

et al. 2017

Biophysical Journal

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The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A$H2B)$(H3$H4) 2 , the tetrasome (H3$H4) 2 , and the disome (H3$H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation. On average, the length of protected DNA in each structure is roughly 18 basepairs per histone protein. Atomistically detailed PANS are used to explain experimental observations; specifically, we discuss interpretation of atomic force microscopy, Fö rster resonance energy transfer, and small-angle x-ray scattering data obtained under conditions when PANS are expected to exist. Further, we suggest an alternative interpretation of a recent genome-wide study of DNA protection in active chromatin of fruit fly, leading to a conclusion that the three PANS are present in actively transcribing regions in a substantial amount. The presence of PANS may not only be a consequence, but also a prerequisite for fast transcription in vivo.

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Section: Resultsmentioning

confidence: 99%

Partially Assembled Nucleosome Structures at Atomic Detail

Rychkov

Ilatovskiy

Nazarov

et al. 2017

Biophysical Journal

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“…The cellular harbour of parvovirus, the dimeric transferrin receptor can bind to only a few of the 60 icosahedrally equivalent sites on capsids (Hafenstein et al, 2007). MD simulations have confirmed the asymmetric transition states of maturation of the tubular and spherical arrangements of hexameric and pentameric oligomers of bacteriophage HK97 and HIV-1 capsids (May et al, 2012;Zhao et al, 2013).…”

Section: Pentameric Ligand-gated and Mechanosensitive Channelsmentioning

confidence: 91%

Asymmetric perturbations of signalling oligomers

Maksay

Tőke

2014

Progress in Biophysics and Molecular Biology

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This review focuses on rapid and reversible noncovalent interactions for symmetric oligomers of tetramers (voltage-gated cation channels, ionotropic glutamate receptor, CNG and CHN channels); pentameric ligand-gated and mechanosensitive channels; higher order oligomers (gap junction channel, chaperonins, proteasome, virus capsid); as well as primary and secondary transporters. In conclusion, asymmetric perturbations seem to play important functional roles in a broad range of communicating networks.

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“…However, obtaining high‐resolution structures of antibody‐antigen complexes may in some cases be challenging, and computational techniques can be used to integrate data from different experimental methods to derive atomic‐level biologically relevant models. In particular, molecular dynamics flexible fitting (MDFF)80 has proven to be an effective method for fitting atomic models into low‐resolution cryo‐EM density maps 81. To create an atomistic model of the glycosylated HIV‐1 Env trimer in complex with antibody CAP256‐VRC269, we used an X‐ray crystal structure of the BG505 SOSIP.664 Env trimer (PDB ID: 4TVP) and of the broadly neutralizing antibody CAP256‐VRC263 (PDB ID: 4OD1) with a negative stain 3D reconstruction of the complex82 along with a combination of homology modeling and MDFF to obtain an atomic‐level model of the complex.…”

Section: Antibodyomics7mentioning

confidence: 99%

“…In particular, highly mobile regions and molecules exposed to solvent are rarely defined structurally, and classical MD has proven to be a valuable tool to probe dynamics of such molecules81, 83, 84, 85. For example, the eight amino acids at the N‐terminal of the fusion peptide of HIV‐1 Env in its closed prefusion state are not visualized in most crystal structures 32, 86, 87.…”

Section: Antibodyomics7mentioning

confidence: 99%

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

Kwong

Chuang

DeKosky

et al. 2017

Immunological Reviews

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SummaryNumerous antibodies have been identified from HIV‐1‐infected donors that neutralize diverse strains of HIV‐1. These antibodies may provide the basis for a B cell‐mediated HIV‐1 vaccine. However, it has been unclear how to elicit similar antibodies by vaccination. To address this issue, we have undertaken an informatics‐based approach to understand the genetic and immunologic processes controlling the development of HIV‐1‐neutralizing antibodies. As DNA sequencing comprises the fastest growing database of biological information, we focused on incorporating next‐generation sequencing of B‐cell transcripts to determine the origin, maturation pathway, and prevalence of broadly neutralizing antibody lineages (Antibodyomics1, 2, 4, and 6). We also incorporated large‐scale robotic analyses of serum neutralization to identify and quantify neutralizing antibodies in donor cohorts (Antibodyomics3). Statistical analyses furnish another layer of insight (Antibodyomics5), with physical characteristics of antibodies and their targets through molecular dynamics simulations (Antibodyomics7) and free energy perturbation analyses (Antibodyomics8) providing information‐rich output. Functional interrogation of individual antibodies (Antibodyomics9) and synthetic antibody libraries (Antibodyomics10) also yields multi‐dimensional data by which to understand and improve antibodies. Antibodyomics, described here, thus comprise resolution‐enhancing tools, which collectively embody an information‐driven discovery engine aimed toward the development of effective B cell‐based vaccines.

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Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics

Cited by 745 publications

References 28 publications

Partially Assembled Nucleosome Structures at Atomic Detail

Partially Assembled Nucleosome Structures at Atomic Detail

Asymmetric perturbations of signalling oligomers

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

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