Vincent P. Conticello

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Name: Conticello, Vincent

Organization: Emory University , USA

Department: Department of Chemistry

Title: Professor(PhD)

Chemicals
References

Structurally Ordered Nanowire Formation from Co-Assembly of DNA Origami and Collagen-Mimetic Peptides

Co-reporter:Tao Jiang, Travis A. Meyer, Charles Modlin, Xiaobing Zuo, Vincent P. Conticello, and Yonggang Ke

Journal of the American Chemical Society October 11, 2017 Volume 139(Issue 40) pp:14025-14025

Publication Date(Web):September 26, 2017

DOI:10.1021/jacs.7b08087

We describe the co-assembly of two different building units: collagen-mimetic peptides and DNA origami. Two peptides CP++ and sCP++ are designed with a sequence comprising a central block (Pro-Hyp-Gly) and two positively charged domains (Pro-Arg-Gly) at both N- and C-termini. Co-assembly of peptides and DNA origami two-layer (TL) nanosheets affords the formation of one-dimensional nanowires with repeating periodicity of ∼10 nm. Structural analyses suggest a face-to-face stacking of DNA nanosheets with peptides aligned perpendicularly to the sheet surfaces. We demonstrate the potential of selective peptide-DNA association between face-to-face and edge-to-edge packing by tailoring the size of DNA nanostructures. This study presents an attractive strategy to create hybrid biomolecular assemblies from peptide- and DNA-based building blocks that takes advantage of the intrinsic chemical and physical properties of the respective components to encode structural and, potentially, functional complexity within readily accessible biomimetic materials.

Self-Assembly of an α-Helical Peptide into a Crystalline Two-Dimensional Nanoporous Framework

Co-reporter:Elizabeth L. Magnotti, Spencer A. Hughes, Rebecca S. Dillard, Shengyuan Wang, Lillian Hough, Arshad Karumbamkandathil, Tianquan LianJoseph S. Wall, Xiaobing Zuo, Elizabeth R. Wright, Vincent P. Conticello

Journal of the American Chemical Society 2016 Volume 138(Issue 50) pp:16274-16282

Publication Date(Web):November 22, 2016

DOI:10.1021/jacs.6b06592

Sequence-specific peptides have been demonstrated to self-assemble into structurally defined nanoscale objects including nanofibers, nanotubes, and nanosheets. The latter structures display significant promise for the construction of hybrid materials for functional devices due to their extended planar geometry. Realization of this objective necessitates the ability to control the structural features of the resultant assemblies through the peptide sequence. The design of a amphiphilic peptide, 3FD-IL, is described that comprises two repeats of a canonical 18 amino acid sequence associated with straight α-helical structures. Peptide 3FD-IL displays 3-fold screw symmetry in a helical conformation and self-assembles into nanosheets based on hexagonal packing of helices. Biophysical evidence from TEM, cryo-TEM, SAXS, AFM, and STEM measurements on the 3FD-IL nanosheets support a structural model based on a honeycomb lattice, in which the length of the peptide determines the thickness of the nanosheet and the packing of helices defines the presence of nanoscale channels that permeate the sheet. The honeycomb structure can be rationalized on the basis of geometrical packing frustration in which the channels occupy defect sites that define a periodic superlattice. The resultant 2D materials may have potential as materials for nanoscale transport and controlled release applications.

Rational Design of Multilayer Collagen Nanosheets with Compositional and Structural Control

Co-reporter:Tao Jiang; Owen A. Vail; Zhigang Jiang; Xiaobing Zuo

Journal of the American Chemical Society 2015 Volume 137(Issue 24) pp:7793-7802

Publication Date(Web):May 28, 2015

DOI:10.1021/jacs.5b03326

Two collagen-mimetic peptides, CP+ and CP–, are reported in which the sequences comprise a multiblock architecture having positively charged N-terminal (Pro-Arg-Gly)3 and negatively charged C-terminal (Glu-Hyp-Gly)3 triad extensions, respectively. CP+ rapidly self-associates into positively charged nanosheets based on a monolayer structure. In contrast, CP– self-assembles to form negatively charged monolayer nanosheets at a much slower rate, which can be accelerated in the presence of calcium(II) ion. A 2:1 mixture of unassociated CP– peptide with preformed CP+ nanosheets generates structurally defined triple-layer nanosheets in which two CP– monolayers have formed on the identical surfaces of the CP+ nanosheet template. Experimental data from electrostatic force microscopy (EFM) image analysis, zeta potential measurements, and charged nanoparticle binding assays support a negative surface charge state for the triple-layer nanosheets, which is the reverse of the positive surface charge state observed for the CP+ monolayer nanosheets. The electrostatic complementarity between the CP+ and CP– triple helical cohesive ends at the layer interfaces promotes a (CP–/CP+/CP–) compositional gradient along the z-direction of the nanosheet. This structurally informed approach represents an attractive strategy for the fabrication of two-dimensional nanostructures with compositional control.

Structurally Defined Nanoscale Sheets from Self-Assembly of Collagen-Mimetic Peptides

Co-reporter:Tao Jiang ; Chunfu Xu ; Yang Liu ; Zheng Liu ; Joseph S. Wall ; Xiaobing Zuo ; Tianquan Lian ; Khalid Salaita ; Chaoying Ni ; Darrin Pochan

Journal of the American Chemical Society 2014 Volume 136(Issue 11) pp:4300-4308

Publication Date(Web):February 26, 2014

DOI:10.1021/ja412867z

We report the design of two collagen-mimetic peptide sequences, NSI and NSII, that self-assemble into structurally defined nanoscale sheets. The underlying structure of these nanosheets can be understood in terms of the layered packing of collagen triple helices in two dimensions. These nanosheet assemblies represent a novel morphology for collagen-based materials, which, on the basis of their defined structure, may be envisioned as potentially biocompatible platforms for controlled presentation of chemical functionality at the nanoscale. The molecularly programmed self-assembly of peptides NSI and NSII into nanosheets suggests that sequence-specific macromolecules offer significant promise as design elements for two-dimensional (2D) assemblies. This investigation provides a design rubric for fabrication of structurally defined, peptide-based nanosheets using the principles of solution-based self-assembly facilitated through complementary electrostatic interactions.

Structurally Homogeneous Nanosheets from Self-Assembly of a Collagen-Mimetic Peptide

Co-reporter:Tao Jiang;Dr. Chunfu Xu;Dr. Xiaobing Zuo; Vincent P. Conticello

Angewandte Chemie 2014 Volume 126( Issue 32) pp:8507-8511

Publication Date(Web):

DOI:10.1002/ange.201403780

Abstract

A collagen-mimetic peptide, NSIII, has been designed with three sequential blocks having positive, neutral, and negative charges, respectively. The non-canonical imino acid, (2S,4S)-4-aminoproline (amp), was used to specify the positive charges at the Xaa positions of (Xaa-Yaa-Gly) triads in the N-terminal domain of NSIII. Peptide NSIII underwent self-assembly from aqueous solution to form a highly homogeneous population of nanosheets. Two-dimensional crystalline sheets formed in which the length of the peptide defined the height of the sheets. These results contrasted with prior results on a similar multi-domain collagen-mimetic polypeptides in which the sheets had highly polydisperse distribution of sizes in the (x/y)- and (z)-dimensions. The structural differences between the two nanosheet assemblies were interpreted in terms of the relative stereoelectronic effects of the different aminoproline derivatives on the local triple helical conformation of the peptides.

Structurally Homogeneous Nanosheets from Self-Assembly of a Collagen-Mimetic Peptide

Co-reporter:Tao Jiang;Dr. Chunfu Xu;Dr. Xiaobing Zuo; Vincent P. Conticello

Angewandte Chemie International Edition 2014 Volume 53( Issue 32) pp:8367-8371

Publication Date(Web):

DOI:10.1002/anie.201403780

Abstract

Controlling Self-Assembly of a Peptide-Based Material via Metal-Ion Induced Registry Shift

Co-reporter:Paolo Anzini ; Chunfu Xu ; Spencer Hughes ; Elizabeth Magnotti ; Tao Jiang ; Lars Hemmingsen ; Borries Demeler

Journal of the American Chemical Society 2013 Volume 135(Issue 28) pp:10278-10281

Publication Date(Web):July 1, 2013

DOI:10.1021/ja404677c

Peptide TZ1C2 can populate two distinct orientations: a staggered (out-of-register) fibril and an aligned (in-register) coiled-coil trimer. The coordination of two cadmium ions induces a registry shift that results in a reversible transition between these structural forms. This process recapitulates the self-assembly mechanism of native protein fibrils in which a ligand binding event gates a reversible conformational transition between alternate forms of a folded peptide structure.

Rational Design of Helical Nanotubes from Self-Assembly of Coiled-Coil Lock Washers

Co-reporter:Chunfu Xu ; Rui Liu ; Anil K. Mehta ; Ricardo C. Guerrero-Ferreira ; Elizabeth R. Wright ; Stanislaw Dunin-Horkawicz ; Kyle Morris ; Louise C. Serpell ; Xiaobing Zuo ; Joseph S. Wall

Journal of the American Chemical Society 2013 Volume 135(Issue 41) pp:15565-15578

Publication Date(Web):September 11, 2013

DOI:10.1021/ja4074529

Design of a structurally defined helical assembly is described that involves recoding of the amino acid sequence of peptide GCN4-pAA. In solution and the crystalline state, GCN4-pAA adopts a 7-helix bundle structure that resembles a supramolecular lock washer. Structurally informed mutagenesis of the sequence of GCN4-pAA afforded peptide 7HSAP1, which undergoes self-association into a nanotube via noncovalent interactions between complementary interfaces of the coiled-coil lock-washer structures. Biophysical measurements conducted in solution and the solid state over multiple length scales of structural hierarchy are consistent with self-assembly of nanotube structures derived from 7-helix bundle subunits. The dimensions of the supramolecular assemblies are similar to those observed in the crystal structure of GCN4-pAA. Fluorescence studies of the interaction of 7HSAP1 with the solvatochromic fluorophore PRODAN indicated that the nanotubes could encapsulate shape-appropriate small molecules with high binding affinity.

Multiple Site-Selective Insertions of Noncanonical Amino Acids into Sequence-Repetitive Polypeptides

Co-reporter:I-Lin Wu;Melissa A. Patterson; Holly E. Carpenter Desai; Ryan A. Mehl; Gianluca Giorgi; Vincent P. Conticello

ChemBioChem 2013 Volume 14( Issue 8) pp:968-978

Publication Date(Web):

DOI:10.1002/cbic.201300069

Abstract

A simple and efficient method is described for the introduction of noncanonical amino acids at multiple, defined sites within recombinant polypeptide sequences. Escherichia coli MRA30, a bacterial host strain with attenuated activity of release factor 1 (RF1), was assessed for its ability to support incorporation of a diverse range of noncanonical amino acids in response to multiple encoded amber (TAG) codons within genes derived from superfolder GFP and an elastin-mimetic protein polymer. Suppression efficiency and protein yield depended on the identity of the orthogonal aminoacyl-tRNA synthetase/tRNA^CUA pair and the noncanonical amino acid. Elastin-mimetic protein polymers were prepared in which noncanonical amino acid derivatives were incorporated at up to 22 specific sites within the polypeptide sequence with high substitution efficiency. The identities and positions of the variant residues were confirmed by mass spectrometric analysis of the full-length polypeptides and proteolytic cleavage fragments from thermolysin digestion. The data suggest that this multisite suppression approach permits the preparation of protein-based materials in which novel chemical functionalities can be introduced at precisely defined positions within the polypeptide sequence.

Fluoroproline Flip-Flop: Regiochemical Reversal of a Stereoelectronic Effect on Peptide and Protein Structures

Co-reporter:Wookhyun Kim;Kenneth I. Hardcastle Dr.

Angewandte Chemie 2006 Volume 118(Issue 48) pp:

Publication Date(Web):16 NOV 2006

DOI:10.1002/ange.200603227

Falsch gefaltet: Die epimeren N-Acetyl-(2R,3R)- und N-Acetyl-(2R,3S)-3-fluorprolinmethylester (1 und 2; siehe Schema) weisen entgegengesetzte Ringfaltungen auf, die die Vorzugskonformationen der 4-Fluorprolinderivate 3 und 4 umkehren. Der Einbau dieser Fluorproline in Proteine ist eine Möglichkeit, die lokale Konformation durch stereoelektronische und sterische Effekte zu steuern.

Fluoroproline Flip-Flop: Regiochemical Reversal of a Stereoelectronic Effect on Peptide and Protein Structures

Co-reporter:Wookhyun Kim;Kenneth I. Hardcastle Dr.

Angewandte Chemie International Edition 2006 Volume 45(Issue 48) pp:

Publication Date(Web):16 NOV 2006

DOI:10.1002/anie.200603227

Pucker up! Structural analysis of the epimeric N-acetyl-(2R,3R)- and N-acetyl-(2R,3S)-3-fluoroproline methyl esters (1 and 2; see scheme) reveals opposing ring puckers that invert the conformational preferences of the corresponding 4-fluoroproline derivatives 3 and 4. Substitution of these fluoroprolines into proteins provides a method for controlling local conformation through stereoelectronic and steric effects.

Cotranslational Incorporation of a Structurally Diverse Series of Proline Analogues in an Escherichia coli Expression System

Co-reporter:Wookhyun Kim;Anna George;Melissa Evans

ChemBioChem 2004 Volume 5(Issue 7) pp:

Publication Date(Web):1 JUL 2004

DOI:10.1002/cbic.200400052

A set of Escherichia coli expression strains have been defined that are competent for the incorporation of a structurally diverse series of proline analogues under culture conditions that are compatible with high levels of analogue substitution within a proline-rich protein substrate. These bacterial strains have been employed to assay the efficacy of incorporation of noncanonical amino acids into a recombinant-protein test substrate and to create variant polypeptides in which native protein sequences have been globally substituted with imino acid analogues in response to proline codons. We envision that these methods may be used to interrogate the effect of imino acid substitution on protein structure and function and may be particularly informative in the context of structural comparison of a series of modified proteins with respect to the stereoelectronic differences between the incorporated proline analogues.

Thermoplastic Elastomer Hydrogels via Self-Assembly of an Elastin-Mimetic Triblock Polypeptide

Co-reporter:E.R. Wright;R.A. McMillan;A. Cooper;R.P. Apkarian;V.P. Conticello

Advanced Functional Materials 2002 Volume 12(Issue 2) pp:

Publication Date(Web):29 JAN 2002

DOI:10.1002/1616-3028(20020201)12:2<149::AID-ADFM149>3.0.CO;2-N

Protein-based analogues of conventional thermoplastic elastomers can be designed with enhanced properties as a consequence of the precise control of primary structure. Protein 1 undergoes a reversible sol–gel transition, which results in the formation of a well-defined elastomeric network above a lower critical solution temperature. The morphology of the network is consistent with selective microscopic phase separation of the endblock domains. This genetic engineering approach provides a method for specification of the critical architectural parameters, such as block length and sequence, which define macromolecular properties that are important for downstream applications.

Thermo-Reversible Self-Assembly of Nanoparticles Derived from Elastin-Mimetic Polypeptides

Co-reporter:T. A. T. Lee;A. Cooper;R. P. Apkarian;V. P. Conticello

Advanced Materials 2000 Volume 12(Issue 15) pp:

Publication Date(Web):28 JUL 2000

DOI:10.1002/1521-4095(200008)12:15<1105::AID-ADMA1105>3.0.CO;2-1

Structural Plasticity of Helical Nanotubes Based on Coiled-Coil Assemblies

Co-reporter:E.H. Egelman, C. Xu, F. DiMaio, E. Magnotti, ... V.P. Conticello

Structure (3 February 2015) Volume 23(Issue 2) pp:280-289

Publication Date(Web):3 February 2015

DOI:10.1016/j.str.2014.12.008

•Nanotubes self-assemble from a 29-residue peptide that contains coiled-coil motifs•Two very different forms can be made using only a single amino acid substitution•Electron cryomicroscopy has been used to achieve near-atomic resolution of one state•This provides insights into the lability of quaternary structure in protein evolutionNumerous instances can be seen in evolution in which protein quaternary structures have diverged while the sequences of the building blocks have remained fairly conserved. However, the path through which such divergence has taken place is usually not known. We have designed two synthetic 29-residue α-helical peptides, based on the coiled-coil structural motif, that spontaneously self-assemble into helical nanotubes in vitro. Using electron cryomicroscopy with a newly available direct electron detection capability, we can achieve near-atomic resolution of these thin structures. We show how conservative changes of only one or two amino acids result in dramatic changes in quaternary structure, in which the assemblies can be switched between two very different forms. This system provides a framework for understanding how small sequence changes in evolution can translate into very large changes in supramolecular structure, a phenomenon that may have significant implications for the de novo design of synthetic peptide assemblies.