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Complex DNA binding kinetics of HIV-1 nucleocapsid proteins

Published on Nov 24, 2014
Abstract
  • References (130)
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References130
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#1Hao Wu (NU: Northeastern University)H-Index: 4
#2Wei Wang (OSU: Ohio State University)H-Index: 43
Last. Mark C. Williams (NU: Northeastern University)H-Index: 35
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Feline immunodeficiency virus (FIV) is a retrovirus that infects domestic cats, and is an excellent animal model for human immunodeficiency virus type 1 (HIV-1) pathogenesis. The nucleocapsid (NC) protein is critical for replication in both retroviruses. FIV NC has several structural features that differ from HIV-1 NC. While both NC proteins have a single conserved aromatic residue in each of the two zinc fingers, the aromatic residue on the second finger of FIV NC is located on the opposite C-t...
5 CitationsSource
#1Divakaran Murugesapillai (NU: Northeastern University)H-Index: 4
#2Micah J. McCauley (NU: Northeastern University)H-Index: 19
Last. Mark C. Williams (NU: Northeastern University)H-Index: 35
view all 8 authors...
The regulation of chromatin structure in eukaryotic cells involves abundant architectural factors such as high mobility group B (HMGB) proteins. It is not understood how these factors control the interplay between genome accessibility and compaction. In vivo, HMO1 binds the promoter and coding regions of most ribosomal RNA genes, facilitating transcription and possibly stabilizing chromatin in the absence of histones. To understand how HMO1 performs these functions, we combine single molecule st...
27 CitationsSource
#1Wei Wang (OSU: Ohio State University)H-Index: 43
#2Nada Naiyer (OSU: Ohio State University)H-Index: 2
Last. Karin Musier-Forsyth (OSU: Ohio State University)H-Index: 46
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During human immunodeficiency virus type 1 (HIV-1) maturation, three different forms of nucleocapsid (NC) protein—NCp15 (p9 + p6), NCp9 (p7 + SP2) and NCp7—appear successively. A mutant virus expressing NCp15 shows greatly reduced infectivity. Mature NCp7 is a chaperone protein that facilitates remodeling of nucleic acids (NAs) during reverse transcription. To understand the strict requirement for NCp15 processing, we compared the chaperone function of the three forms of NC. NCp15 anneals tRNA t...
16 CitationsSource
#1Carolin A. Guenzel (Paris V: Paris Descartes University)H-Index: 5
#2Cécile Hérate (Paris V: Paris Descartes University)H-Index: 5
Last. Serge Benichou (Paris V: Paris Descartes University)H-Index: 28
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Like other HIV-1 auxiliary proteins, Vpr is conserved within all the human (HIV-1, HIV-2) and simian (SIV) immunodeficiency viruses. However, Vpr and homologous HIV-2, and SIV Vpx are the only viral auxiliary proteins specifically incorporated into virus particles through direct interaction with the Gag precursor, indicating that this presence in the core of the mature virions is mainly required for optimal establishment of the early steps of the virus life cycle in the newly infected cell. In s...
52 CitationsSource
#1Kathy R. Chaurasiya (NU: Northeastern University)H-Index: 5
#2Micah J. McCauley (NU: Northeastern University)H-Index: 19
Last. Mark C. Williams (NU: Northeastern University)H-Index: 35
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HIV-1 replication is inhibited by the enzyme APOBEC3G via two separate mechanisms. A deamination mechanism requires rapid binding and release of single-stranded DNA (ssDNA), whereas a roadblock mechanism requires slow binding. Now APOBEC3G has been shown to initially bind ssDNA with rapid on–off rates. The enzyme subsequently converts via oligomerization to a slowly dissociating binding mode, which, it is proposed, inhibits reverse transcription.
48 CitationsSource
#1Xinghua Zhang (NUS: National University of Singapore)H-Index: 9
#2Hu Chen (NUS: National University of Singapore)H-Index: 14
Last. Jie Yan (NUS: National University of Singapore)H-Index: 34
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Double-stranded DNA (dsDNA) unconstrained by torsion undergoes an overstretching transition at about 65 pN, elongating the DNA to about 1.7-fold. Three possible structural transitions have been debated for the nature of DNA overstretching: (i) “peeling” apart of dsDNA to produce a peeled ssDNA strand under tension while the other strand coils, (ii) “inside-strand separation” of dsDNA to two parallel ssDNA strands that share tension (melting bubbles), and (iii) “B-to-S” transition to a novel dsDN...
72 CitationsSource
#1Hao Wu (NU: Northeastern University)H-Index: 4
#2Mithun Mitra (OSU: Ohio State University)H-Index: 10
Last. Robert J. Gorelick (SAIC: Science Applications International Corporation)H-Index: 47
view all 8 authors...
Abstract The human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) protein plays an essential role in several stages of HIV-1 replication. One important function of HIV-1 NC is to act as a nucleic acid chaperone, in which the protein facilitates nucleic acid rearrangements important for reverse transcription and recombination. NC contains only 55 amino acids, with 15 basic residues and two zinc fingers, each having a single aromatic residue (Phe16 and Trp37). Despite its simple structure...
30 CitationsSource
#1Graeme A. King (VU: VU University Amsterdam)H-Index: 14
#2Peter Gross (VU: VU University Amsterdam)H-Index: 6
Last. Erwin J.G. Peterman (VU: VU University Amsterdam)H-Index: 43
view all 6 authors...
Mechanical stress plays a key role in many genomic processes, such as DNA replication and transcription. The ability to predict the response of double-stranded (ds) DNA to tension is a cornerstone of understanding DNA mechanics. It is widely appreciated that torsionally relaxed dsDNA exhibits a structural transition at forces of ∼65 pN, known as overstretching, whereby the contour length of the molecule increases by ∼70%. Despite extensive investigation, the structural changes occurring in DNA d...
85 CitationsSource
#1Micah J. McCauley (NU: Northeastern University)H-Index: 19
#2Emily M. Rueter (Mayo Clinic)H-Index: 5
Last. Mark C. Williams (NU: Northeastern University)H-Index: 35
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Eukaryotic High-Mobility Group B (HMGB) proteins alter DNA elasticity while facilitating transcription, replication and DNA repair. We developed a new single-molecule method to probe non-specific DNA interactions for two HMGB homologs: the human HMGB2 box A domain and yeast Nhp6Ap, along with chimeric mutants replacing neutral N-terminal residues of the HMGB2 protein with cationic sequences from Nhp6Ap. Surprisingly, HMGB proteins constrain DNA winding, and this torsional constraint is released ...
30 CitationsSource
#1Thayaparan Paramanathan (UMN: University of Minnesota)H-Index: 6
#2I. Vladescu (UMN: University of Minnesota)H-Index: 6
Last. Mark C. Williams (UMN: University of Minnesota)H-Index: 35
view all 5 authors...
Actinomycin D (ActD) is a small molecule with strong antibiotic and anticancer activity. However, its biologically relevant DNA-binding mechanism has never been resolved, with some studies sug- gesting that the primary binding mode is intercal- ation, and others suggesting that single-stranded DNA binding is most important. To resolve this con- troversy, we develop a method to quantify ActD's equilibrium and kinetic DNA-binding properties as a function of stretching force applied to a single DNA...
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