Enhancement of protein modeling by human intervention in applying the automatic programs 3D-JIGSAW and 3D-PSSM

Bates, Paul A.; Kelley, Lawrence A.; MacCallum, Robert M.; Sternberg, Michael J.E.

doi:10.1002/prot.1168

Cited by 514 publications

(341 citation statements)

References 21 publications

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“…The cloning vector pHBc encoding the full-length (amino acids 1-183) of HBc protein, subtype ayw, with inserted BamHI restriction site at MIR was constructed by M. Mihailova like those described in another study. 29 Three-dimensional predictions of the reconstructed HBc structures were performed on the basis of the x-ray structure of the HBc, genotype A, 7 by a comparative modeling program 3D-JIGSAW (http://bmm.cancerresearchuk.org/3djigsaw/) 30 and presented by Chimera software (Figure 1, B, C). 31 The fragments of BBK32 gene-encoding amino acids 130 to 166, 160 to 175, and 153 to 175 (BF130-166, BF160-175, and BF153-175 constructs, respectively) were amplified by PCR from B. burgdorferi sensu stricto isolate B31 DNA sample.…”

Section: Methodsmentioning

confidence: 99%

“…18 FN is a large glycosylated mosaic protein composed of multiple copies of three types of modules: FNI, FNII, and FNIII. These modules comprise several functional domains that mediate interactions with cell-surface receptors (integrin-binding tripeptide, Arg-Gly-Asp [RGD] peptide), other ECM components (e.g., two heparin-binding domains, the Predictions were performed on the basis of the x-ray structure of the HBc, genotype A, 7 by a comparative modeling program 3D-JIGSAW (http://bmm.cancerresearchuk.org/3djigsaw/) 30 and presented by Chimera software. 31 Chains A (orange red) and D (cornflower blue) of the HBc asymmetric tetramer unit are presented, but B and C chains are omitted for visual clarity.…”

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confidence: 99%

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Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

Ranka¹,

Petrovskis²,

Sominskaya³

et al. 2013

Nanomedicine: Nanotechnology, Biology and Medicine

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Virus-like particles (VLPs) are created by the self-assembly of multiple copies of envelope and/or capsid proteins from many viruses, mimicking the conformation of a native virus. Such noninfectious nanostructures are mainly used as antigen-presenting platforms, especially in vaccine research; however, some of them recently were used as scaffolds in biotechnology to produce targeted nanoparticles for intracellular delivery. This study demonstrates the creation of fusion VLPs using hepatitis B core protein-based system maintaining a fibronectin-binding property from B. burgdorferi BBK32 protein, including the evidence of particles' transmission to BHK-21 target cells via caveolae/rafts endocythosis. These results make this construct to be an attractive model in development of HBc-based nanoparticles for cellular targeting applications and highlights the fragment of B. burgdorferi BBK32 as a novel cellular uptake-promoting peptide.From the Clinical Editor: This paper discusses the nanotechnology-based application of self-assembling viral-like peptides (VLP-s) for targeted delivery using a hepatitis B core protein based system. Creating fusion VLPs may be an attractive model for cellular targeting applications. © 2013 Elsevier Inc. All rights reserved.Key words: Fibronectin; Nanoparticles; B. burgdorferi Various strategies in the design of nanoparticles (NPs) -particles in the size range 1 -1000 nm -aim to create new generations of drug-delivery vehicles, contrast agents, and diagnostic devices. 1 One of the relevant potentials of the nanomedicines is their intracellular targeting possibility. Effective intracellular drug delivery is important for therapeutic agents that have specific molecular targets inside a cell as well as for drugs that undergo extensive efflux from the cell by the efflux transporters. Thus, the ability to penetrate inside cells bypassing lysosomal degradation is one of the key problems in the rational design of pharmaceutical nanocarriers. 2 For this purpose, the surface of nanocarriers could be modified by certain internalizable ligands (e.g., folate, transferrin) or by cellpenetrating peptides, such as a trans-activating transcriptional activator (TaT), an integrin-binding peptide (RGD peptide) or polyArginine. 3 This approach is receiving increasing attention over the last years because it is efficient for a range of cell types, and various endocytotic mechanisms can be engaged to facilitate the internalization of a carrier. 2 Virus-like particles (VLPs) is a broad group of nanocarrier systems that exhibit great potential in biomedicine research, including targeted drug delivery. 4 VLPs are self-assembling noninfectious supramolecular structures that have been produced from structural proteins of a wide variety of virus families. The unique features of VLPs are proper dimensions for nanoscale applications, size homogeneity, a large surface area-to-mass ratio, a symmetric macromolecular organization, biodegradability, biocompatibility and ease of production/ purification. 5 In addit...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

Ranka¹,

Petrovskis²,

Sominskaya³

et al. 2013

Nanomedicine: Nanotechnology, Biology and Medicine

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“…In the automatic mode, the program looks for homologous templates in the sequence databases and splits the query amino acid sequence into domains. This process can take up to an hour, depending on the load of the system [17]- [19]. …”

Section: B Tertiary Structure Determination By Homologymentioning

confidence: 99%

Novel Chimeric Protein as Therapeutic Vaccine against Hepatitis B Virus

Kizilbash¹,

Hai²,

Alruwaili³

2013

IJBBB

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“…65 This program predicts structures based on their sequence homology with proteins whose structural coordinates are already deposited in the PDB. A possible structure for the complex of a scFv and a b-spectrin segment was obtained by docking the two proteins manually, and restrained by molecular information obtained from experimental data.…”

Section: Structural Predictionmentioning

confidence: 99%

Apparent structural differences at the tetramerization region of erythroid and nonerythroid beta spectrin as discriminated by phage displayed scFvs

et al. 2011

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We have screened a human immunoglobulin single-chain variable fragment (scFv) phage library against the C-terminal tetramerization regions of erythroid and nonerythroid beta spectrin (bI-C1 and bII-C1, respectively) to explore the structural uniqueness of erythroid and nonerythroid b-spectrin isoforms. We have identified interacting scFvs, with clones ''G5'' and ''A2'' binding only to bI-C1, and clone ''F11'' binding only to bII-C1. The K d values, estimated by competitive enzyme-linked immunosorbent assay, of these scFvs with their target spectrin proteins were 0.1-0.3 lM. A more quantitative K d value from isothermal titration calorimetry experiments with the recombinant G5 and bI-C1 was 0.15 lM. The a-spectrin fragments (model proteins), aI-N1 and aII-N1, competed with the bI-C1, or bII-C1, binding scFvs, with inhibitory concentration (IC 50 ) values of~50 lM for aI-N1, and 0.5 lM for aII-N1. Our predicted structures of bI-C1 and bII-C1 suggest that the Helix B 0 of the Cterminal partial domain of bI differs from that of bII. Consequently, an unstructured region downstream of Helix B 0 in bI may interact specifically with the unstructured, complementarity determining region H1 of G5 or A2 scFv. The corresponding region in bII was helical, and bII did not bind G5 scFv. Our results suggest that it is possible for cellular proteins to differentially associate with the C-termini of different b-spectrin isoforms to regulate a-and b-spectrin association to form functional spectrin tetramers, and may sort b-spectrin isoforms to their specific cellular localizations.Keywords: beta spectrin; erythroid and nonerythroid; scFv; structural difference; affinity difference Abbreviations: aI-N1, a recombinant protein of aI-spectrin segment with residues 1-156; aI-spectrin, erythroid a-spectrin; aII-N1, a GST fusion protein of aII-spectrin segment with residues 1-147; aII-spectrin, nonerythroid a-spectrin; bI-C1, a GST fusion protein of bI-spectrin segment with residues 1898-2083; bI-C1D, a GST fusion protein of bI-spectrin segment with residues 1898-2070, that is, the residues 2071-2083 in bI-C1 were deleted; bI-spectrin, erythroid b-spectrin; bII-C1, a GST fusion protein of bII-spectrin segment with residues 1906-2093; bII-spectrin, nonerythroid b-spectrin; CD, circular dichroism; CDRs, complementarity determining regions; ELISA, enzyme-linked immunosorbent assay; EPR, electron paramagnetic resonance; GST, glutathione S-transferase; HRP, horseradish peroxidase; ITC, isothermal titration calorimetry; PBS, phosphate buffered saline at pH 7.4; rG5, recombinant G5, a single-chain variable fragment found to bind bI-C1; scFv, single-chain variable fragment.Yuanli Song's current address is

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Enhancement of protein modeling by human intervention in applying the automatic programs 3D-JIGSAW and 3D-PSSM

Cited by 514 publications

References 21 publications

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

Novel Chimeric Protein as Therapeutic Vaccine against Hepatitis B Virus

Apparent structural differences at the tetramerization region of erythroid and nonerythroid beta spectrin as discriminated by phage displayed scFvs

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